الأمراض الوراثية الأحادية الجين الصبغية الجسدية السائدة

بحث متقدم

أ ب ت ث ج ح خ د ذ ر ز س ش ص ض ط ظ ع غ ف ق ك ل م ن هـ و ي

الأمراض الوراثية الأحادية الجين الصبغية الجسدية السائدة

امراض وراثيه احاديه جين صبغيه جسديه سايده

-

??????? ???????? ???????? ????? ??????? ??????? ???????

?. ???? ?????

??????? ???????? ???????

??????? ?????? Marfan syndrome

??????? ????? ?? ?????? ?????, ???? ????? ??????? ????? 2-3/10000 ???????.

??????? ????????

????? ?????? ??????? ?????? ? ??????? ??????? ????? ?? ????? ????? ??????? ? ???? ????? . ???? ???? ?? 30 ?????? ?????? ??????? ??????? ???????? ??????, ??? ??? ????? ??????? ????????? ??? ????? ?????? ??????? ?? ?????? ?????? ?? ???? ??????? ?? ?? ??????ǡ ? ???? ??????? ??????? ??????? ??? ???? ??????? ?????? .

1- ????? ?????? ???????:

????? ?????? ?????? ?? ???????? ???????? ?????? ??????? ????? ????? ?? ?????? ??????? ??????? ????????????? ??????? ???????? ???? ?????? ??????? ?(????? 1)? ????? ????? ?????? ???????? ????? (?????? ??????? arachnodactyly) ? ???????? ??? ?????? ???????? ?????????? ???? ?? ??? ????? . ?? ????? ?????? ?? ???????? ???????? ?????? ????? ???????? ???? ?????? ???? ???????? ???????? ? ????? ?? ???? ??? ??? ??????? ?? ??? ??????? ???????? genetic background. ???? ?????? ??? ??? ?????? ??????? ??????? ??? ?????? ??????? ?????? ??????????? ????????? (????? 2).

?? ???? ????? ????? ?????? ?????? ?????? ??? ????? ????? (pes planus). ???? ??????? ?????? ??????? ????? ?????? ?????? ???????? ????????? ? ????? scoliosis ?? ??????? kyphosis ?????? ?????? pectus excavatum ?? ??? ??????? (????? ???????) pectus carinatum.

2- ????? ?????? ?????? ???????:

???? ??????? ??????? ????????? ???? ??????? ?????? ??? ????? ???? ??????? sinuses of Valsalva? ??????? ????? ?????ѡ ????? ?????? ?????? ??? ??? ???? ?????? ????? ?????? ????? ????ݡ ????? ??????? ?????? ??????.

3-??????? ????????:

????? ???? ??????? ???????? ???????? ?????? ?? ??? ?????. ??? ?????? ?????? ectopia lentis (?????? 3)

???? ?????? ??????? ???????? ??????? ????? ???? ??? ?? ????? 60٪ ?? ???????? ??? . ??? ???? ????? ?? ????? ?? ?????ۡ ??? ???? ???? ??????? ?????ޠ ?? ??????? ????? ?????? ?? ??????? ?????? ?????? ???? ???????? ???.

4- ????? ?????? ???????:

?? ???? ???????? ??????? Lung bullae ?? ???? ?????? ????, ????? ?? ???? ??? ???????? ????? ?????? spontaneous pneumothorax.

5- ????? ?????? ??????:

?? ???? ????? ??????? ?? ??????? ??????? ??????? (???? ??????? dural ectasia)? ??? ?? ????? ??? ???? ?????? ??????? ???????. ????? ??????? ?????? ?? ???? ????? ?????? ?? ????? ?????? ?? ????ޡ ?????? ?????? ??? ???? ???????? ? ????? ?? ????? ??????? ????????? ?????????.

????? ????????

???? ??????? ?????? ?? ?????? ?????? ????? ?? ??????? ?? ??? ?????????-1 fibrillin-1 (FBN1) ??????? ??? ?????? q21.115. ????? ??????????-1 ????? ?? ???????? ?????????-1 ? ?? ?????? ???? ??????? ?????? ????? ???? ???????? ????????? microfibrils. ???? ???????? ????????? ????? ?? ??????? fibers ???? ???? ????? ???????? ??????? ??????. ????? ??? ??? ????? ???????? ????????? ?????? ???? ????? ????? ?????? ?? ????? ?????? ??????? ??? ????? ?????? ??????? ???????? ?? ???? ????? ?????. ???? ?? ???? ??????? ?? ??? FBN1 ?? ???? ?????????-1? ?????? ??????? ?????? ???????? ????????? ????? ???? ???? ??? ?????? ??????? ?????? ???? ??? ????? ????? ????? ??? ??? ???? ????? ??????? ?? ?????? ?? ??????ɡ ??? ???? ??? ??? ??? ??????? ???? ?????????.

???????

???? ??????? ?????? ??????? ???????? ??? ????? ???????? ?????????? ??????? ?? ????? ????? ????????. ???? ????? ???? ??????? ?????? ???? ???? ???????? ?? ????? ??????? ?????? ???? ????? ????? ????? ????????? ????????. ?? ?????? ?????????? ??????? ???????? ??? ????? ?????? ??? ?????ɡ ???? ???? ????? ??? ????? ????? ?FBN1 ?? ????? ??? ??????? ?? ??? ????????? ??????? heterogeneity .

???????

??? ??? ????? ???????? ??????? ?????? ?? ????? ????? ??????? ?? ?????? ??? ?? ???? ??? ??? ?????? ??????? ??????ɡ ??? ???? ????? ?????? ??? ????? ??????. ??? ??????? ?? ????????? ?????? ?? ???? ?????? ?? ??? ???? ?? ?????֡ ????? ??????? ???????? ??? ??? ?????? (??? ??????? ??????) ?????? ???? ???? ??????? ??????.??? ????? ??????? ???? ???? ??????? ????Ƞ ???????? ??? ?????????? ??????? arrythmias? ???????? ?? ???? ????? ????ȡ ?????? ??? ????.

??????? ???????? ?????? ???????? ??????

??????? ?????? ?? ?????? ????? ???? ???? ????. ???? ????? 75٪ ?? ??????? ?? ????? ???? ?? ??? ???????? ?? ??? ???? 25٪ ?? ??????? ?? ???? ?????do novo. ????? ??????? ???? ????? ??? ???? ?????? ??? ??? ????????, ???? ??? ??? ???????? ??????? ??????? ????? ???? ?? ????? ?? 50٪. ??? ??? ??? ????? ?????? ??????? ?????? ???????? ??? ?????? ?? ????? ???? ???? ????? ????? ????֡ ??????? ????? ?????? ??? ????? ?? 50٪ ????? ???? ?? ????? ??????? ????? ?? ??????? population risk ???? ?????? ???? ?????? (??????????) ?? ??????? ??????? (???????) germline ??? ????? ?????. ????? ?????? ?????? ????? ?????? ?? ??????? ?????? ??????? ???????? ?????? ????? 50٪ . ? ???? ????? ??????? ?? ??? ??????? ?? ????? ????? ??????? ??????ɠ ??? ???? ?????? ??????? ???????? ?????? ??????? ?? ??????. ???? ??????? ?????????? ??????? ??? ??????? preimplantation genetic testing ????? ??? ?????? ??????? ?????? ???????.

?????? 1. ????? ????? ???????? ??????

?????? 2. ????? ??????? ?? ???? ??????? ??????

?????? 2. . ?????? ?????? ectopia lentis ?? ??????? ??????

???????? ?????????? ?????????? (????? 1) ?Neurofibromatosis Type I

??? ???? ?????? ???? ??? ??????? ????? ????? ?????? 1/3000-4000 ???????.

??????? ????????

?????? ?????? ?????? (????? 1) Neurofibromatosis Type ?? ??? ????? ?????ѡ ???? ???? ?????? ????? ????? ??? ??????? (?? ?? ????? ???????)? ???? ???? ?????? ?? ??? ???? ???? ???? ?????? ?????? ????? ???? ???????? ?????????. ??? ???? ?????? ???????? ?????????? ?????????? (????? 1) ???? ???? ????? ?? ???? ?? ???????? ????????? ???????:

1- ??? ?????? ??????? (?? ?? ????) ????? 5 ?? ?? ???? ?? ?????? ??? ?????ۡ ?? ????? 15 ?? ?? ???? ?? ?????? ??? ?????? (?????? 1).

2- ????? ????? ????? ?? ?? ??? (????? ?? ????) (?????? 2)

??? ??? ???? ???? ????? ????? (???? ?? ????) (?????? 3).

3- ??? freckling ???? ?? ????.

4- ??? ???? ???? Optic glioma.

5- ?????? ??? Lisch nodules (?????? ?? ????) (??? ???? ???? iris hamartomas) (?????? 4).

6- ???? ????? ????? ??? ??? ???? ????? ?????? sphenoid dysplasia ?? ?????? ???????? ?????? tibial pseudarthrosis.

7- ???? ???? ?? ?????? ?????? (???? ?? ?? ?? ???) ???? ??????? ?????? ?????? (????? ?????).

???? ?????? ?????? ?????? ??????? ?????? ???????? ?????? ?????? ???????? ???? ?????? ?????? ????? ??????? ?????? ?????? ??? ?????. ???? ???? ?????? ??????? ?? ???? ??????? ???????? ???? ???? ?????? ?????? ??????? ??? ???????? ???? ?????? (ADHD) ?? 50-75٪ ????. ???? ????? ??????? ?? ?????? ????? ???? ??? ?? ???? ??? ??????? ???????? ???? ???? ?? ?? ???. ???? ??????? ??????? ????? ??? ??????? ??? ?? ?????? ?? ?????? ?? ????? ?????.

???? ????? ????? ??????? ??????? ???????? ??????? ?????? ?????? NF1 ??? ?????? ????? ????? ??? ?? ???? ??? ??????? ????????.

????? ????????

???? ?????? ?????? ?????? ?? ???? ??????? ??????? Heterozygous ?? ??? NF1 ???????? ??? ?????? ??????? ?? ?????? 17 (17q11.2) ??? ???? ???????? ???? ?????????????? neurofibromin ???? ???? ????? ????? tumor suppressor. ???? ??????? ?? ??? NF1 ????? ?????? ??? ???? ?? ????? ?? ????? ???????? ?????? ??????. ????? ????, ????? ??????? ??????? ??????? ??? ??? ??????? ?? ???? ?????. ?????? ???? ???? ??? ?????? ??????? ????????? ?????? ??? ????? ??? ????.

???????

????? ?????? ?????? ?????? ???????? ??? ????????? ????????. ?????? ?? ???? ???????? ???????? ???????? ?????? ???????.

???????

?????? ?????? ?????? ??? ????? ????? ???? ???? ?????? ???????. ???? ????? ??? NF-1 ?? ????? ???? ????? ??? ??? ?????? ????? ?????? ??? ????? ????ɡ ????? ??? ??????? ????????? ???????? variable expressivity. ??? ???? ?????? ?? ???? ??? ??? ??????? ?? ????֡ ???? ???? ??????? ??? ????? ????? ?????? ??????? ??????.

?? ???? ????? ??????? ??????? ?????? ?? ?????? ?? ???????? ??????? ??????? ?? ??????? ??????? ??????? ??????? ???????ɡ ??????? ??????? ?? ??? ???????. ??? ???, ???? ??????? ???? ????ɡ ?? ?????? ???? ????, ????? ?????? ?? ?????? ???? ?????? ?????? ???? ?????.

???????

???? ??????? ???? ????????? ???? ????? ????? ?? ?????? ?????? ?? ?????? ?????? ??????? ??????? ??????? ?? ?????? ??????ɡ ????? ???? ????????? ??????? ???????? ?? ??????? ??????? ???????? ?? ??????? ??????? ??????? ??? ????? ??????. ???? ??????? ??????? ??????? ??? ????? ?????? ????? ???? ?? ?? ??? ????? ??????? ???????. ?????? ?? ????? ????? ??????? ???????.

??????? ???????? ?????? ??????? ?????? ?????? (????? 1)

???? ???????? ?????????? ?????????? (????? 1) ??????? ????? ????? ?????. ???? ??? ????? ??? ??? ??????? ????? ????? ????? de novo ?? ????? ?NF1. ? ??? ????? ?????? ?????? ?????? ?? ???? ???NF1 ????? 50%? ???? ?????? ??????? ???????? ????? ???? ???ѡ ??? ???? ?????? ???????. ? ???? ??????? ??????? ?? ??? ??????? ?? ????? ????? ????? ??????? ??? ???? ?????? ??????? ????? ?????? ?? ??????.

Figure 1.

?????? 1. ??? ?????? ???????

Figure 2.

?????? 2. ????? ????? ?????

?????? 3. ??? ???? ???? ????? ?????

?????? 4. ?????? ??? Lisch nodules

?????:?????? ?????? ?????? ?????? Tuberous Sclerosis?? ?????? ????? ???? ??? ?????? ?? ??????? ??????? ?? ????? ????? ?? ?????. ????? ????? 1/6000 ???????.

??????? ????????

1- ?? ?????

??? ????? ?? ?? ???????? ??????? ??????. ????? ??????: ????? ????? ?????? Hypomelanic macules (??? ????? ?????? ash leaf spots) (90% ?? ???????) (?????? 1)

?????? ?????? ????? ??????? confetti skin lesions (?????? 2)

?? ??????? ??????? ???????? angiofibromas ??????? (??? ??? ???? ?adenoma sebaceum) (75% ?? ???????) (?????? 3)

??????? ??????? shagreen patches (50% ?? ???????) (?????? 4).

2- ????? ?????? ?????? ???????

????? ????? 50٪ ?? ???? ?????? ?????? ?? ?????? ?????? ????? ?????? ??? ?????? ?????ɡ ?????? ???????? ?? ?? ??? 25٪ ? 61٪ ?? ???????? ?????? ??????? ?? ?????? ????? ??? ???????? (??????) autism. ?????? ????? ????? ??? 2008 ?? ?????? ?????? ????? self-injurious behavior ?? ??? ?? 10٪ ?? ??????? ????? ?????? ?? ?????? ??????. ??? ???? ?? ???? ???????? ?????? ???? ??? ???? ???????? ???? ?????? ADHD? ?????????ɡ ???????? ??????. ? ???? ???? ?????? ??? ???? ???? ?????? ???????? ???????? ??????? ?????????? MRI ????.

??? ????? ?????? ?????? ??????? ????? ??????? ??????? ???????? ?? ?????? ?????? ????? ???????? ??? ??????? ??????? subependymal nodules? ???? ?????? ????? ??????? cortical dysplasias? ???????? ??????? ???????? ??????? ??? ??????? ??????? subependymal giant cell astrocytomas (?????? 5)

?????? ???? ??????? ???????? ?????? ??????? ??????. ?? ???? ??? ??????? ??????? ???????? ??????? ??? ???? ?????? ????? ? ???????? ???????? ?????? ???? ??????? ????????. ????? ???? ?? 80% ?? ?????? ?? ??????? ???????.

3- ??????? ???????:

???? ????? 60-80% ?? ?????? ???? ???? ???? ?????? ?????? ?????? ??????? angiomyolipomas (AML) ??????? ?? ???? ???? ?????? ???????.? ????? ????? 20-30٪ ?? ???????? ??????? ?????? ?? ????? ????? ???? ???? ??? ???????.

4- ??????? ???????:

???? ??????? ??????? ??????? rhabdomyomas ?? 47-67% ?? ???? ?????? ?????? ?? ?????? ??? ??????? ?? ???? ????? ??? ????? ?????. ??????? ?? ???? ??? ??????? ????? ???? ???? ?? ??? ???????.

5- ??????? ???????:

???? ????? ??????? ?????? ?????? ?????? Lymphangioleiomyomatosis ?? ??????? ?? ?????? ??????? ??????? ??? ??? ??? ???? ?? ????? 30 -40٪ ?? ?????? ???????? ??????? ??????.

6- ??????? ???????:

???? ??????? ?? ?????? ?????? ???????? ??????? hamartoma ? ?? ????? ??? 30-50٪ ?? ??????.

????? ????????

???? ??? ?????? ?????? ?? ???? ????? ?? ????????

TSC1 ?TSC2 ?????? ?????? ?? ??????? ???????? ???? ???? ????? tumor suppressor genes.. ????? ???? ????? ?? ????? ???? ???? ???? ?? ?? ????? 20٪ ?? ?????? ?? ??? ????? ????? ???????? ?????????? ??????? ???????.

???????

????? ????? ?????? ?????? ??? ????????? ????????. ????? ????? ???????? ????????? ??????? ??????? ????? ?? 75٪ -90٪ ?? ??????? ????? ??????? ???????? ???????? ?????? ?????? ??????. ??? ??? ????? ?????? ????? ?? ????? ?????? ?????? ????? ??? ??? ???????? ?? ???? TSC1 ?TSC2 ?? 31٪ ?69٪ ?? ?????? ??? ???????.

???????

????? ????? ????? ??? ??? ??????֡ ????? ???? ???? ???? ????? ????? ??? ??? ?????? ??????? ???????? ??????? ???? ?? ???? ??????? ????ǡ ?????? ??????. ????? ??????? ????? ?????? ?? ?????? ????? ???? ???? ????? ?????ɡ ?? ??? ???? ??????? ??????? ??????? ????? ?????? ?? ??????? ???????. ? ?? ??? ????? ????? ??? ???? ??????? ???????? ???? ????? ??????? ???? ???????? ??????? ?????? ????????.

???????

?????? ??????? ???? ????? TSC ?????? ?? ????? ??????? ??????. ????? ?????? ???? ???? ??????? ???????ɡ ???? ?????? ??????? ??? ???? ??? ????? ???? ??????? ???????. ????? ?????? ?????? ??? ??????? ??????? ??? ??????֡ ???? ???? ??????? ?????? ?????? ????? ?? ??????? ??? ????? ???????.

??????? ???????? ?????? ??????? ??????

???? ?????? ?????? ?????? ????? ????? ?????. ???? ?????? ?????? ?? ???? ?????? ?????? ????? ????? de novo. ?????? ?? ??? ????? ????? ?????? ?????? ??????? ?????? ?????? 50%. ??? ???? ?????? ??????? ????? ?????? ?? ?????? ???? ??????? ??????? ?? ??? ??????? ?? ????? ????? ????? ???????.

?????? 1. ????? ????? ??????

?????? 2. ???? ?????? ????? ??????? confetti skin lesions

?????? 3. ??????? ??????? ???????? ???????

?????? 4. ????? ??????? Shagreen patches

?????? 5. ??????? ??????? ?????? ??????? ??? ??????? ??????? subependymal giant cell astrocytomas

?????:??? ????????? ???? ???????

???? ???? ????? ???????? ??????? 1/200-500 ??? ???????? ??????? ??? 1/160000-1000000.

??????? ????????

???? ??? ??????????? ??????? Familial Hypercholesterolemia ??????? ??????? ??????????? (??????? ???????????? ????? ??????? low-density lipoprotein (LDL)) ????? ????? ????? ?????? ?????. ????? ?????? ???????? ??????? ?? ?????? ?????? ???????????? ?? ????? ?????? ?? ????? ??? ??? ????? (??????? ???? ??????? ??????? ??????? xanthelasma palpebrarum) (?????? 1)?

???????? ???????? ??????? (??????? ???? ????? ??????? ??????? arcus senilis corneae) (?????? 2)?

???????? ?? ??????? ????????? ????????? ????????? ??? ???? ?? ??? ???? (??????? ???? ????? ?????? ????? tendon xanthoma) (?????? 3).

???? ????? ???? ?????????? ?? ????? ???????? ??? ???? ???????? ??? ????? ?????? ???? ????? ????? ???????? ???????. ???? ??????? ?????? ????? ?? ??? ??????????? ??????? ?? ???? ????? ???????? ??????? ?? ???? ??? ?????? ??????? angina pectoris ?? ??????? ??????? heart attacks ?? ?? ???? ????? ??? ?? ????? ?? ???? ??????. ?

???? ????? ?? ??? ??????????? ???????:

1- ????? ?????? ??????? Heterozygous ????? ?? ???? ????? ?? ???? ??????? LDLR, ApoB , PCSK9 ????? ???? ????? ?? 60-80% ?? ????? ??? ??????????? ???????.

2- ????? ???????? ??????? homozygous ????? ?? ?????? ?? ???? ??????? ??????? ?? ???? ????? ?? ????? ?????? ?????. ??? ????? ???? ???? ????? ???? ???????? 1/160000-1000000.

????? ????????

???? ????? ??? ??????????? ??????? ????? ?? ????? ??? LDLR???? ???? 60-80% ?? ??????ʡ? ???? ???( ApoB 1-5%) ????? ???(PCSK9 0-3%).

1- ????? ??? ?LDLR LDL receptor ???? ?????? ??????? ?? ?????? 19 (19p13.1-13.3-) . ????? ???? ?? ??? ???? ??????. ?? ???? ?????? penetrance ??? ?????? 90% ??????? ???????? ???????.

2- ????? ??? APOB: ??? ?????? ??????? ?? ?????? 2 (2p24-p23) ? ???? ?????? ??? ?????? ?? ???? ??? ??????????? ??????? ??????? ??????? ??? ???.

3- ????? ??? PCSK9 (proprotein convertase subtilisin/kexin type 9) ??? ?????? 1 (1p34.1-p32) ? ???? ????? ?????? ??? ???????? LDL ??? ??????? ???????.

???????

??? ??? ?????? ????? ?????? ??? ??????????? ??????? ? ???? ?? ???:

1- ??? ????????? ???? ??????: ??? ???? ?????? ??? ??????????? ??????? ?? ??????? ????? ????? ????????? ???????:

?- ?? ??? ??????????? ??????? ???????? ???????:

- ?? ???????? ??? ?????????: ??????? ????? ?? ???????????? ????? ?????C (LDL-C) : >190 ???/?? [> 4.9 ?????/???] ?? ??????? ?????????? ????? >310 ???/?? [>8 ?????/???]?

- ?? ??????? ??? ????????? ?? ?????????: ??????? ?LDL-C <160 ???/?? [4.1 ?????/???] ?? ??????? ?????????? ????? >230 ???/?? [> 6 ??????/???]).

?- ??? ??????????? ??????? ???????? ???????: ??????? ?????????? ????? ???? ???? ???? ??? ??????? >500 ???/??????? (>13 ??????/???).

2- ??? ?????? ???? ???? ???? ???? ???? ????? ???????? plaque ?? ???????? ??????? ???????? ???? ??? ????????.

3- ????????? ?? ????? ???????: ????? ??????? ?????? ??????? ??????? (??? ???? ????? ????? ???? ?????? ?? ???? ??????? ?? ?????? ?? ????? ???? ????? ????? ??????? ??? ?? ??????? ?????? ????? ????? ??? ?? 45 ????).

4-???? ??????? ????? ??????? ??? ????? ??? ???????? ???? ??????? ?? ??? ???????.

5- ???? ???? ?? ??? ????? ??? ?????? ?? ??? ??????????? ???????.

???????

1- ????? ???????? ???????: ???? ??? ???? ????? ???????? ???????20 ???? ?? ??????? ???????? ???? ??????????? ??????? ??? ??????? . ????? ??????? ????? 50٪ ?????? ???? ????? ????? ????? ?? ??? ????? ???? 50 ????? ?? ?????? ??? ?????????. ??? ?????? ??? ????????? ?????? ????? ??? ???? 30٪ ???? 60 ?????.

2- ????? ???????? ???????: ????? ???? ??????? ???????? ???? ????? ?? ?????? ????? ????? ??? ?? ????? ????????? ?? ?????. ????? ????? ?? ?????? ?????? ???????? ??????? coronary bypass ??? ????? ???????? ?????. ??? ???? ???? ???? ?????? ??????.

???????

1- ????? ???????? ???????: ????? ??? ??????????? ??????? ??????????? Statins. ???? ?????????? ??????? ??????????? ????????????? ????? ??????? LDL? ??? ????? ?? ??? ?? ??? ??????? ????? ??? ????? ????? ????. ????? ???????? ?? ?????? ??? ??????????? ??????? ????????? ???? ??? ????? ?? ??????? ??????? ?? ????? ????? ??????? ????? 48٪ ?? ???? ?????? ??? ???? ?????? ?? ????? ????? ?????????? ???????? ???? ???? ??????? ??????? ???????? ????? ?????? ????? ??????. ???? ????? ???????? ???? ????? ????? ?????? ?? ??? ??????????? ??????? ??????? ????????? ??????? ???????????.

2- ????? ???????? ???????: ????? ????? ??? ????? ???? ????ɺ ?? ???? ???????? LDL ?? ?????? ?????? ?? ?? ??? ??????? ?????? ??????. ???? ??????? ??????? ?? ?????????ʡ ????????? ?? ????? ????? ??? ?????? ?? ????? ??????? ??????. ??? ?? ???? ?????? ????? ?? ??? ??????? ??????????? ?? ???? ???? ??????? ????? ?LDL? ??? ??? ?????? LDL ?? ???? ???? ?? ????? ???? ?????? dialysis. ???? ????? ????? ?? ??????? ??????? ????? ??? ???? ????? ????? ?? ???????? LDL ?????? ??????ɡ ????? ??? ??? ???? ??????? ??????????? ?? ???? ????? ????ǡ ???? ???? ????? ???? ??????? ??? ?? ??? ??????? ?????? (??? ????֡ ??????????ʡ ?? ?????? ???????? ??????? ??????? ?????? ?????) .

3- ???????: ??? ??? ??? ??????????? ??????? ????? ??? ??????? ? ???? ???? ???????? ?? ??? ???? ?? ?????ɡ??? ?? ??????? ??????? ???? ?????? ???????? ?? ??? ????????? ???????? ???? ???? ????? ????????. ?? ???? ?????? ?? ??????? ????? ????? ????? ???????? ??????? ?????? ????? ???????? Bile acid sequestrates ?????????????? ?feno fibrate????? ????? ?? ???????. ?? ??ߡ ???? ?? ?????????? ???? ?????ɡ ????? ????????? ?? ??????? ?????? ??? ??? ?? ????? ?? ??????.

??????? ???????? ?????? ???? ??????????? ???????

??? ??????????? ??????? (?????? ???????? ????????? ???????) ?? ?????? ????? ???? ???? ???? ????? ??? ??? ???????? ??????? ?? ???? ??????? ???????. ?? ??? ????? ???? ???? ??????????? ??????? ????? ?? ??? ???? 50٪.

??? ??? ??? ???????? ?????? ???? ??????????? ??????? ???????? ??????? ????? ?????? ??????? ???? ??????????? ??????? 75٪ (?? 50٪ ?????? ??????? ???? ??????????? ??????? ???????? ??????? ? 25٪ ?????? ??????? ???? ??????????? ??????? ???????? ???????).

???? ????? ??????? ?? ??? ??????? ?????? ????? ????? ??????? ??? ?? ????? ?????? ??????? ?? ??? ????? ?????? ???? ???? ??????????? ??????? ???????? ??????? (?? ??? ?? ????? ??? ???????? ????????? ?? ??? ????? ?????? ???? ???? ??????????? ??????? ???????? ???????) ??? ?? ??? ????? ??? ????.

?????? 1. ??????? ??????? ??????? xanthelasma palpebrarum

?????? 2. ????? ??????? ?? ??????? arcus senilis corneae

?????? 3. ????? ?????? ??? ????? tendon xanthoma

?????_??? ??????? ???????? ????? ??????? familial adenomatous polyposis (FAP) ?????? ???? ?????? ??? 1/7000 ??? 1/22000.

??????? ????????

???? ????? ??????? ????????? ???????? ?????? ?? ??? APC:

1-? ??? ??????? ???????? ????? ??????? Familial AP ????????: ??? ??? ????? ????? ??? ???? ?? 100? ????? ???? ??? ??????? precancerous ???? ?? ????? ??????? ???? ?????. ???? ???? ???? ???? 16 ??? (?????? ????? ??? 7-36 ???). ????? ???? ???????? ?????FAP ?????? ?? ??????? ??? ??????? ???? ???? ??? ?? 40 ?????.

?????? ???????:

?- ??? ??? ??????? ?? 100 ?????? ??????? ???????? ???ɡ ???? ??? ?????? ?? ???? 100 ?? ???? ?? ??????? ????????? ?????????? ??? ?????? ???? ??????? ???????? ????? ???????. ?? ????? ?????????? ??????? ??? ??????? ??? ?? ????? ??? ???? ??? ??????? ???????? ????? ??????? (FAP) ???? ??? ??????? ??????? ?????? MUTYH (MAP- MUTYH-associated polyposis) (??? ??? ????? ??? ????? ????? ????? ???? ????) ????? ????? ??????? ????????? ???????? ?????.

?- ??? ?? 100 ????? ???? ?? ???? ??? ???? ???? ???? ??????? ???????? ????? ???????.

2- ??? ??????? ???????? ????? ??????? ????????? attenuated FAP: ????? ?????? ????? ??????? ?????? ??????? ????? ??? ??????? ????????? ??? ??? (?????? ??? 10 ?99) ? ????? ??????? ?? ???? ????? ???? ????? ????? ??????? ?? ?? ?????? ??? ???? ?????? ??????? ??? ?? ????.

??????? ??????? ????????:

?- ????? ??? ??????? ?????? ?????? ??? 10 ??? 99: ????? ????? ?? ??????? ????? ????? 100 ?? ???? ?? ??????? ???? ???? ?? ??????? "????????" (35 ??? 40 ??? ?? ????) ?? ???? ????? ??? ??????? ???????? ????? ??????? ???????.

?- ???? ????? ???? ?????? ??????? ????????? ??? ?? 60 ????? ?????? ????? ???? ??????? ????? ???????.

3- ??????? ?????? Gardner syndrome: ????? ????? ??????? ????????? ????????? FAP ????? ??? ??? ?? ??????? ??????? osteomas ?????? ??????? ??????.

4- ??????? ????? Turcot syndrome: ??? ????? ??????? ????????? ?? ??????? ??????? ????????.

????? ????????

????? ??????? APC ??????? ???? ????? ??? ?????? ?????? (5q21) ??? ?????? ???? ???? ???? ????? ???? ??? ??????? ???????? ?? ????? ??????? ????????? ???????? ???? APC. ?? ????? ??? ????? ??? ?????? ??????? ??? ?? ?? ???? ?? ????? ?????? metaphase ?? ???????? ???????mitosis. ???? ???????? APC ??????? ????? ?????? ??????̠ ?? ????? ???????. ???? ?? ????? ??????? APC ?????? ????? truncated ??? ?????. ???? ????? ??????? ???????? ???????? ????? ???? ?????.

???????

????? ??????? ?? ?????? ????? ??? ????????? ????????. ???? ?????????? ??????? ???????? ???? APC ?? ???????? ??????? ????? ?? ?? ??? ??? 90٪ ?? ??????? ???????? ???? ??????? ???????? ????? ??????? ????????. ?????? ?? ?????? ?????????? ???????? ?? ??????? ?????? ?????? ?????? ???????? ????ѡ ????? ?? ????? ????? ??? ??????? ???????? ????? ??????? ?? ??? ??????? ???????? ????? ??????? ?????? ?? ?????? ??? ????????? ???? ?????? (??? ???? ??????? ????? ??????? ?????? <100).

????? ??? ?????????? ?? ?????? ??? ??????? ????? ??????? ?? ????? ?????? ????? ?? ????? ?????? ?????? ?????? ?????.

???????

????? ????? ??????? ?????? ???????? ???? ??????? ???????? ????? ??????? ??? ??????? 42 ????? ????? ????? ??????? ??? ?? ???? ??? ????? ????????? ???????? ???????.

?? ???????? ?????? ?????? ?????? ?? ?????? ????? ???? ??? ??????? ??????? ?? ??????? ?????? ?????? ?????? ???????? ???????? desmoid tumor? ???? ?? ????? ?? ?? ????? ???????? ?????? ?????? ??? ???????????? ??????? ??????? ????? ??? ????? ????? ??????? ???.

???????

???? ???????? ??????? colectomy ????? ???? ??? ??????? ?????? ???? ?? 20 ?? 30 ??? ???? ??????? ??????? ?????????? (?????? ???????? ??? ???????????? NSAIDs) ????? ???????? sulindac ?????? ??????? ?????? ?? ??? ??????? ???????? ????? ??????? ??????? ??? ??????? ???? ????? ???????? ?? ??????? ???????? ?? ???????? ?? ??????? ????? ?????? ?? ??????? ??????? ??? ????? subtotal. ???? ????? ??????? ??????? ?????? ???????. ? ????? ??????? ???????? ??????? ?????????? ?? ????? ????????ʡ ?? ?????? ????? ??????????? ?? ?????? ????????? ????? ??????ǡ ?? ???????.

??????? ???????? ?????? ???? ??????? ???????? ????? ???????

???? ??? ??????? ???????? ????? ??????? ???? ????? ???? ???? ????. ???? ??? ???????? ?????? ?? ????? 70-80% ?? ??????. ??? ????? ?????? ???????? ???? ??????? ???????? ????? ??????? ????? ?????? ?????? 50٪ ?????? ?????? ??????? ?????. ??? ???? ???????? ??????? ?? ??? ??????? ???????? ??????? ??? ??????? PGD ?????? ??? ?? ?????? ?????? ?????? ?? ??? ????? ??????? ????????.

?????_????? ??????? ????????? ?????????? ??????? Hereditary Non-Polyposis Colon Cancer (HNPCC) ???? ????? ???? ??? ???? Lynch syndrome? ???? ??? 140000 ???? ????? ?? ????? ??????? ????????? ?? ?? ??? ?? ???????? ???????. ??? 3 ??? 5 % ?? ??? ????????? ????? ????? ??????? ????????? ????????? ???????.

??????? ????????

???? ????? ??????? ????????? ????????? ??????? ??????? ??? ??????? ?????? ??????? ?????? ????? ????? ??????? ??????? ???????? ??????ɡ ??????? ????????? ??????? ??????? ??????? ??????. ???? ???? ???? ????????? ?? ??????? ????? ?????? ?? ????? ??????? ????????? ????????? ??????? ???????: 52٪ -82٪ ?????? ??????? ????????? (????? ????? ??? ??????? 44-61 ???)? 25٪ -60٪ ?????? ????? ????? ?? ?????? (????? ????? ??? ??????? 48-62 ???)? 6٪ ??? 13٪ ?????? ?????? (????? ????? ??? ??????? 56 ????)? ? 4٪ -12٪ ??????? ?????? ?????? (????? ????? ??? ??????? 42.5 ??ɡ ???? ????? ?? ????? ?? 30٪ ??? ?? 40 ????).

????? ????????

???? ????? ??????? ????????? ????????? ??????? ?? ????? ?? ??? ????? ????? ??? ??????? mismatch repair ???????? (MLH1, MSH2, MSH6, PMS2)? ????? ??????? ??????? ?? ??????? ???? ???? ??? ??????? ?????? ?????? microsatellite instability (MSI). ???? ???? ??????? ?? ??????? ?? ????? ???????? ???????? ??????????? ?? ??? ????????? ????????? (?????: CACACACACA ...). ???? ???????? ?? ??????? MLH1 ? MSH2????? 90% ?? ???????? ??????? ?????? ??????? ????????? ????????? ???????? ???? ???? ???????? ?? MSH6 ????? 7-10% ??? PMS2 ??? ?? 5%.

???????

???? ??????ՠ ????? ??? ?????? ???? ?????? ???????? Amsterdam criteria ?????? ????? ??????? ????????? ?????????? ???????:

?- ?????? ???????? I:

1-???? ?????? ?? ???? ?? ????? ?????? ???? ???? ????? ??????? ?????????? ???? ???? ?? ?? ????? ?????? ?????? (????? ?????? ??) ??????? ??????? ???????.

2- ???? ????? ???????? ?????? ??????.

3- ???? ???? ?? ???? ?????? ??????? ????? ??? ?? 50 ?????.

4- ??????? ??? ??????? ???????? ????? ??????? FAP.

?- ?????? ???????? II

1- ????? ?? ???? ?? ????? ?????? ?????? ?????????? ???????? ?????? ??????? ????????? ????????? ??????? HNPCC? ???? ???? ?? ???? ?? ?????? ?????? ?? ????????.

2- ???? ????? ???????? ?????? ??????.

3- ???? ???? ?? ???? ????????? ???????? ?????? ??????? ????????? ?????????? ??????? ????? ??? ?? 50 ?????.

4- ??????? ??? ??????? ???????? ????? ??????? FAP.

???????

?????? ??????? ?????? ??????? ????????? ?????????? ??????? ????? ??? ???????? ??????? ?????? ??????? ???????? ?????? ?? ?????? ??????? ????????. ?? ???? ???? ??? ?????????? ??????? ??????? ??? ???? ????? ??????? ??????? ??????? ?? ????? ??????? ??????? ?????? ??????? ????????? ?????????? ??????? ??? ????? ??????? ???????? ?? ????? ????? ????. ???? ??? ????????? ??????? ????? ???????? (??? ???? ???????) ???????? ??? ???????? ?? ????? ???????.

??????? ???????? ?????? ?????? ??????? ????????? ?????????? ???????

???? ????? ??????? ????????? ????????? ??????? ?????? ????? ????? ?????. ??? ?????? ?????? ?????? ????? ????? ??????? ????????? ????????? ??????? ????? ?? ??? ????????. ??? ??? ????? ???????? ??? ????? incomplete penetrance? ???? ??? ???? ??? ??????? ???????? ? ?? ???? ???? ?? ????? ??????? ???????? ????? ??? ?? ????? ?????? ?????? ?????? ?????? ??? ???? ????? ???? ????ǡ ???? ???????? ?? ???? ??? ????? ?????? ????? ????? ???? ?? ??? ??????? ???????? ?????? ??????? ????????? ????????? ??????? ?????? ????????. ????? ?? ??? ????? ??????? ?????? ??????? ????????? ????????? ??????? ?????? ??????? ????? 50٪. ??????? ??? ??????? ???? ?? ????? ?????? ??????? ??????? ??? ??? ?????? ?????? ??????? ?? ??????. ? ??????? ?? ??? ??????? ??? ?????? ??? ??? ??? ??????? ???? ???? ???? ?? ????? ??????? ????? ?????? ?????? (??? ????? ??????? ????????? ????????? ???????).

?????_???? ??????? Polydactyly ???? ?????? 1 ?? ?? 500 ????? ???.

??????? ????????

???? ??? ????? ?? ?? ????? ?? ?? ??? ??????. ???? ?????? ???????? ???? ???? ????? ?? ??????? ?????? ???? ???? ??????ǡ ?????? ?? ????? ??? ????? ??? ??????? ?? ??? ???????? ?????? ?Ǡ ???? ?????? ?????? ?????. ????? ?????? ??????? ????? ??? ?????? ?????? (80% ?? ???????) (?????? 1)? ?????? ??? ?????? ??????? (???? ??????? ??? ?????? preaxial ) (?????? 2)? ????? ???? ?? ??????? ??????? ??????. ?????? ?? ???? ?????? ???????? ???? ?? ???? ?????ɡ ??????? ?? ???? ?? ????? ??? ???? ?????? ????????.

1- ???? ??????? ???????: ????? ?? ???? ???? ??????? ??????? ?????? ?????? ? ??????? ?????? ??????? syndactyly ?? ???????. ???? ??????? ??? ??????(?????? ??????) ?? ?????? ????? ???? ?? ??????? ????? ???????ɡ ????? ??? ??????? ??? ?????? ??????. ???? ??????? ??????? ??? ?????? ?? ???? ?????? ?? ???????? ???????? ?????? ??????????? ?????????? ?????????? Mongoloids ??? ???? ?????? ?? ??????? ??????. ??? ???????? ????? ???? ??????? ??? ?????? ?? ??????? ????? ?? ???? ???????? ?????? ?????? ??????? ????? ??????.

2- ???? ??????? ????????: ??? ??????. ???? ??? ?????? (????? 1/3000) ??? ???? ?????? ???? ???? ???? ?? ??? ??????.

3- ???? ??????? ????????: ????? ?????ˡ ??? ??? ???? ????? ?? ?????? ?? ?????? ?? ???????. ???? ??? ?????? ??????? ???? ??? ???? ??????.

????? ????????

????? ???? ??????? ?? ????? ?????ɡ ????? ??????? ?? ????? ???? ?? ?? ?????. ??? ?? ??????? ?? ??????? ??????? ???????? Hox-a ??? Hox-d ?? ???? ??? ???? ???????. ?????? ??????? ?? ????? HOXD13 ?? ???? ??????? ??????? synpolydactyly. ??? ??ߡ ?? ??? ?????? ??? ??????? ???????? ?? ??? ??????? ???????? ????? ???????.

?? ????? ???? ??????? ?????ǡ ? ?????? ?????? ???? ?????? ???? ???????? ??????. ??? ???? ????? ???? ??????? ????? ????? ?? ???? ??????ʡ ?? ???? ???? ??? ?????? ??????? multifactorial trait. ???? 97 ??????? ?????? ?????? ?? ????? ?????? ?? ???? ???????.

1- ???? ??????? ???????: ???? ???? ??????? ??????ɡ ???? ???? ?????? ???? ???? ???? ?? ???? ????? ?? ???????. ?? ?????????? ???? ???? ?? ???? ??????? ??????? ????: ??????? ????? Meckel syndrome ???????? ????

2- ???? ??????? ????????: ??????? ?? ???????? ??? ??????? ???? ????? Holt?Oram syndrome ???????? Fanconi anemia.

3- ???? ??????? ????????: ?????? ?? ???????? ??? ????? ????? ?????.

???????

??? ????? ???????? ???????? ??????? ??????? ????? ????? ???????.

???????

1- ???? ??????? ???????: ???? ??? ????? ???? ??? ????? ?? ????? ?????? ??????? ?? ?????? ??? ??????? ?????? ???????.

2- ???? ??????? ????????:??? ???? ?????? ????????? ???????(??????? ????????) ??? ?????ɡ ??? ????? ???? ???? ????? ???? ???? ????. ?????? ?? ??? ??????? ??????ɡ ?? ?? ?? ?????? ??? ????ϡ ???????ѡ ???????? ???????? ???????? ?????? ??? ??????? ????????. ????? ???????? ?? ????? ?????? ?? ????ѡ ???? ?? ??? 9 ? 15 ????? ?? ?????.

3- ???? ??????? ????????: ????? ?? ??? ?????? ?? ??? ???? ??? ??? ??? ????? ?????? ????? ?????? ???? ???????ʡ ??? ?????? ????? ??????.

??????? ???????? ?????? ????? ???????

???? ???? ??????? ???????? ?????? ????? ?????. ? ????? ?? ??? ?? ??? ????? ???? ????? ??????? ???????? ?????? ????? ????? 50٪.

?????? 1: ???? ??????? ???????

?????? 2: ???? ??????? ????????

?????_??? ???????? (HD) Huntington Disease ???? ????? ???? ???????? Huntington Chorea , ???? 3-7 ?? ?? 100000 ?? ?????????? ??? ??? ?????? ?? ???? ??????? ??????????? ????????? ?????????.

??????? ????????

??? ???????? ?? ?????? ???? motor? ????? cognitive???? ????. ????? ????? ??? ??? ??????? 35 ??? 44 ??? ?????? ?????? ?? 15 ??? 18 ??? ??? ?????? ??? ???? ?? ???? ?? ?? ?? ?? ??????? ??? ???????ɡ ??? ????? ???? ??????? ??? ??? ?? 50 ???? ?? ?? ????? 25٪ ?? ???? ???????? ??? ??? ???? ??? ??? ?? 70 ?????, ????? ????? ?????? ?? ??? ????ա ????????? ?????ɡ ???? ????ڡ ???? ?????? ???? ??? ????? ???? ????? ?????? ?????? ?? ?????? ??????????.

??? ???? ?????? ??? ??????? ?? ??? ???? ??????:

1- ????? ???? ???? ??? ????? ????? ?? ????? ??????? ???????? ?????: ???? ????? ?? ???? ?? 90٪ ?? ??????? ??? ?????? ???? ??? ????? ????? ?? ????? ??? ?????ɡ ???? ????? ?? ??????? ?? ?????? ?? ????ڡ ??? ????? ????? ??? ??? ?????. ????? ????? ???? ??????? ????? ?????? ?? ??? ???????. ????? ????? ????? ???? ????? ????????١ ? ?? ???? ??????? ?????? ????? ???? ???????. ???? ????? ?? ?????? ???? ??? ??? ?????? bradykinesia ? ?????? rigidity? ???? ?????? dystonia ?? ?????? ?? ??? ?????. ???? ??? ?????? Dysarthria ?? ??? ???? ??? ????. ??? ???? ??? ????? Dysphagia ?? ??????? ????????. ???? ??? ????????? Hyperreflexia ?? 90٪ ?? ??????? ?? ??? ???? ????? clonus ?????????? ???????? ??????? extensor plantar responses ?? ??? ????? ??????? ???.

2- ?????????? ??????? ??? ?? ??? ??????? ???????? ????????? ?? ??????ɡ ?/ ?? ????????: ???? ?????? ???? ????? ?? ??????? ???????? ?? ???? ???? ??? ????????. ????? ???????? ???????? ???????? ???? ?????? ??????? ???? ??????? ????????? ???????? visuospatial?? ???? ?????? ??? ??????? ?? ??????? ???????? acquired knowledge. ???? ?????? ?? ???????? ???? ????? ??????? ???? ??? ????? ???? ???? ???? ??????? ???????.

???? ??? ??????? ?? ??? ???? ?? ?????? ?????? ??? ??????? ?????????. ????? ??? ??????? ?? ??? ???????? ???? ??? ??? ????? ??? ?? ???? ?? ??? ????????.

???? ??????? ????? ?? ??????? ??? ??????? ???????? ???? ????????? ??? ???? ??????? psychosis ?????? ????? ?? ??? ?????? ??????? schizophrenic psychosis. ??? ?????????? ???????? ??????? ?????? ?????????? ???????? intermittent explosiveness? ????? ??????apathy? ?????????? aggression? ???????? ?????? alcohol abuse? ?????? ??????????? ??????ɡ ?????? ??????. ??????? ????????? Delusion paranoid ?????? ??? ??????? Hallucinations ??? ??? ??????.

????? ??????? ????????? ??? ?????? ?? ??????? ??? ???????? ???? ????????? ???? ?? ??????????ɠ ???????? ?? ??????? ?????????. ? ???? ???? ???????? ?? ??? ???????? ??? ?????. ???????? ???????? ?? ???????? ?????? ????? ?? ???????? ???? ?????.

3- ??????? ??????? ???? ?????? ?? ????? ?????? ???????.

????? ????????

????? ??????? ??????? ??? ?????? ?? ??? ???????? ?? ????? HTT . ?? ???? ??? ???????? ???????? ??????????? CAG ?? ??????? ????? ?? ??? ????? ?? ?????? ?????? ?????? ???? ???????. ???? ??? ??? ???????? CAG ?? ??????? ???????? normal alleles ?? ??? ?? 26? ??? ??? ??? ????? ??? 27 ?35 ????? ??? ??????? ??????? Intermediate alleles. ??? ??? ????? ??? ?????? ??????? ???? ????? ????? ??? ???????? ???? ???? ??? ????????? ?? ???? CAG ???? ????? ?????? ??? ?? ???? ??? ?? ?????? ?????? ???? ???????? (?? ???? ?? 36 ?????). ??? ?? ???? ??????? ??????? ???? ??????? HD-causing alleles ????? ????? ??????? CAG 36 ?? ????. ???? ????? ????? ??? ??????? ????? ????? ?????? ?????? ???? ??????? ?????? ??? ????? ???? ??????.

???????

????? ????? ??? ???????? ??? ????? ???????? ????????ɡ ?????????? ???????? ??????ɡ ?????? ?? ????? ??? ???????? ?????? ??????????? CAG ?? 36 ?????? ?? ??? HTT.

???????

??? ??? ???? ???? ????????? ???? ???? ?????? ????? ???? ?? ??? ??? ??????. ????? ?????? ??????? ?????? ?????? ??????? (??????????? haloperidol)? ??????? ?????? ??? ??????? (???????????? olanzapine)? ???????????????? benzodiazepines? ?? ??????? ????????? ???????? ???????? monoamine depleting agent ??????????????? tetrabenazine ??????? ??????? ???????. ?????? ?????? ???????? anti-parkinsonian agents ????? ??? ?????? hypokinesia ?????? rigidity. ?????? ??????? ??? ??????? ???????? psychotropic drugs ?? ??? ????? ???????? ??????? ????? ??????? ?????????? ??????? (???????ȡ ???????? ???????ɡ ????? ?????????)? ??????? ??? ?????????? valproic acid ????? ??? ?????? ?????? myoclonic hyperkinesia.

??????? ???????? ?????? ???? ????????

???? ??? ???????? ?????? ????? ?????. ??? ????? ?????? ???? ???????? ????? ???? ?????? ?????? ????? ?????? 50٪ ?????? ?????? ??????. ???????? ??????? Predictive testing ?? ???????? ???????????? ?????? ????? ?????? ??????? ?????? ????? ???? ????? ?????? ??????? (??? ?? ??? ??? ???? ????????? ???????? ?? ????? ?? ??? ??????) ???? ?? ???? ????? ?? ???? ???? ????????. ??? ??ߡ ??? ??????? ???????????? ????????? ??????? ?????? ???????? ?? ??????? ????????. ?? ????? ???????? ??????? ??????? ??????? ???????????? ???????? ????? ?????? ??? ??????? ?? 18 ?????. ??????? ?? ??? ??????? ?? ???? ???????? ??????? ??????? ???? ??????.

?????:???? ????? ?????? Osteogenesis Imperfecta .???? ????? ???? ????? ?????? ?????? brittle bone disease ?? ??????? ???????? Lobstein syndrome.? ????? ????? 2-5 ?? ?? 100000.

??????? ????????

?????? ???? ????? ?????? ???? ?????ɡ ??????? ????? ???? ??? ?????? ???????? communicating hydrocephalus? ????????? ??????? basilar invagination? ?????? ??????ɡ ??????? ??????? (?????? 1)?

?????? ????ڡ ?????? ?? ?????????. ???? ?? ???? ?????? ????? ????? ?? ??????? ??????? ????? ?????ɡ ?????????.

???? ????? ????? ?? ???? ????? ?????? ???? ??? ????? ??????:

?(?????? 2)

????? ?????: ????? ????????? ?? ??? ????? ?? ???? ?????.

????? ??????: ????? ?????? ?? ???? ?? ??? ??????? perinatally lethal .

????? ??????: ???? ????? ?????? ?????? ???????.

????? ??????: ???? ????? ?????? ?? ???? ??????.

?? ???? "?????? ??????" ???? ????? ?????? ? ????? ??????? ??? ???? ??? ?? ??????? ????????.. ????? ????:

? ?????? ??? ???? ?? ?? ???? ????? ???? ?? ??? ??? ???? ????? ????? ??? ??? ???????? ?? ????? ?? ????? ??????.

? ??? ?????? ?? ???? ???? ??? ??? ??????? ??? ???? ??? ????? ?????? ??? ????????? ?? ???? ?????? ?? ???? ?? ???????.

? ??? ?????? ?????? ?? ???????.

? ???? ??????? ?????? (DI) ?Dentinogenesis imperfect.

? ????? ????? ???????? ?? ????? ?? ??? ??????.

? ????? ??????? Ligamentous laxity ?????? ?? ?????? ???? ?????? ?????

? ??? ?????? ????? ????? ?????ա ??? ???? ?? ????? ????? ????? ????? ????.

????? ????????? ???????? ?? ???:

1- ???? ?? ????? ?????? ???? ??????ɡ ????? ?? ???? ?? ??????? ?? ?????? ??????? ?????? ???? ????? ?? ??????? ????????.

2- ????? "??? ????" "codfish" vertebrae ? ??? ???? ???? ????? ?????? ?????????? ?? ?????? ??????? ????? ???? ??? ????????.

3- ?????? ??????? wormian bones ?

4- ????? ?????? Protrusion acetabuli ??? ???? ??? ???? ???? ?????? ???? ??????? ???? ?? ????? ?????.

5- ??? ????? osteopenia ?? ????? ????? osteoporosis ???? ????? ??? ?????? ???? ???? ?????? ?????? ??????? ?? ?????? ???????? (DEXA).

????? ????????

???? ??????? ?? ?????? COL1A1 ? COL1A2 ???? ???? ????? ??????. ????? ????? COL1A1 ??? ?????? 17 ???? ??????? ???? ??????? ????- ?????? ????? ????? ?????? (??????? ????? ??????? ??????? ???????) ?????? ????? Osteoporosis. ??? ????? COL1A2 ?????? ??? ?????? 7q21.3 ????? ??????? ???? ??????? ????- ?????? ????? ????? ?????? ?????? ????? ???????? ?????? ????????? atypical Marfan syndrome.

???????

????? ????? ???? ????? ?????? ???:

1- ????? ???????ɡ ??? ?????? ???????ɡ ?????????? ???????? ???????.

2- ????????? ???????? (???? ??? ????? ?????? ?????? ???? ?????ɡ ??????? ??????? ? ????? ??? "????" ? ??? ????? .

3- ?????????? ??????? ???????? ?? COL1A1 ?COL1A2 ?/?? ??????? ????????? ?????? ????????? ?? ????? 1. ???? ??????? ????????? ?????? (?? ????? ???? ????? ????????? ?? ????? ????? ?????? ?? ??????? ?? ????? ????? ??????? ??????? ??????? dermal fibroblasts) ?? ???????? ?????? (84- 98٪ )?? ???? ??????? ??????? ???? ????? ?? ??? ?????.????? ?????????? ??????? ??????? COL1A1 ?COL1A2 ?? ???? ?? 90٪ ?? ?????????? ?? ?????? ????? ?????? ?? ????? ???? ????? ?????? ???????.

???????

????? ??????? ???????? ??????: ????? ??????? ?????? ??????? ?????? ????????? ?? ??????? ?????ɺ ?????? ?????? ?????? ??????ȡ ?????? ??????? ?????? ?????? ??????? ??????? ??????? ?????? ?????? ??????? ?????? ?????? ??? ?????ɡ ???? ?????? contracture ????? ???????? ?? ?????? ?????? ??????. ?????? ????? ?????? ??? ??????. ??? ??????? ?? ?????? ???????? ??????? ???? ??????? intramedullary rodding.

????????? ????????

???? ???? ????? ?????? ?????? ????? ????? ?????. ????? ???? ??????? ???? ?????? ??????? ??????? ?? ??????? COL1A1 ?? COL1A2 ???? ??? ????? ????? ?? ??? ????? ???? ???? ????? ???? ????? ?????? ?????? 50٪ ?????? ?????? ????? ??? ????? ???? ????? ??????.?? ?????? ??? ??????? ????? ??????? ?? ????ʠ ?????? ??????? ????? ?????? ?????????? ??????? ??? ?? ?????? ??? ????? COL1A1 ?? COL1A2 ?? ???? ????. ???? ?? ???? ????? ???????? ??? ???????(????? ?????), ??? ???? ?? ???? ?? ?? ???? ?? ????ՠ ????? ????? ?????? _?? ???? ?? ????? ??????? ?????? ????? ??????ɠ ??????? ??? ????? 20 ?? ????? ??? ??? ????? ?? ??????? ???????? ?? ??? ???? ?? ????? ?? ???? ???? ???? ?? ?????? . 3-5% ?? ???????. ???? ?? ???? ????? ???? ???? ????? ???? ????? ?????? ?????? ?????? ??? ????? ???? ????? ??????. ???? ?? ???? ??????? ?? ??? ??????? ?? ????? ????? ??????? ????? ?????? ?????????? ???????? ?? ???? ?? ????? ???? ????? ??????, ?? ???? ?? ????? ??????? ??????? ?? ??? ??????? ??????? ??? ??? ??????? 20 ?? ????? ??? ??? ????? ?? ??????? ?????? ???????? ?? ??? ???? ?? ????? ?? ???? ???? ???? ?? ??????.

?????? 1: ?????? ???????

?????? 2: ??????? ???????? ????? ????? ??????

?????:??? ????? ??????? ???? ????? ?????? ??????? 1/8000 ??? ???????.

??????? ????????

????? ??? ????? ??????? ????? ????? ??????? ???????. ? ???? ?? ???? ??????? ????? ?????? ?? ??? ???????? ?????? ????? ?????? ????? (???? myotonia) ?? ?????? ??? ?????? ??? ????? ????? ????? ??? ?????????, ???? ???? ??????? ?? ??? ?????? ????? ?? ????? ????? ?? ??? ???? ?????, ??? ???? ?????? ???????? slurred speech ??? ??????? ???????? ?? ?? ???? ??? ???? ?????.

??? ??? ????? ? ?????? ????? ?????? ??????? ????? ????? ??????? ?????? (?? 90% ?? ???????) ? ?? ???? ???????? ????????? ?? ?????? ???????? ??? ????? ?????? ? ??? ?????. ???? ?? ????? ????? ??? ????? ?? ????????? ?? ?????????? ?? ????? ??? ??? ???? ?? ???? ?? ?? ???. ????? ??? ?????? ??? ???? ???? ??? ?????? ???????? ??? ??? ?????? ?? ????? ?????.

???? ????? ??????? ?? ??? ????? ???????: ????? 1 ?????? 2. ?????? ?????? ?????? ???? ???????? ??? ????? ?? ?? ????? ????? 2 ???? ??? ?? ???? ???? ???????? ?? ????? 1. ???? ??? ??????? ?? ????? 1 ?????? ??????? ??????? ?????? ??????. ??? ??? ??????? ?? ????? 2 ????? ?? ?????? ????? ????? ????? ???????? ????????? ????????. ???? ???? ??????? ?? ?????? ?????? ?? ????? ?? ????? ??????. ?????? ??????? ?? ?????? ?????????.

??? ??? ???? ????? ??????? ????????? ??????ɡ ???????? ?????????? ?? ??????. ??? ????? ??? 200 ???? ?? ????? 1? ???? ?????? ??????? ???????? ??????? ?? ?????? ???????? ???? ??? ???? ?????? ???? ??? 27٪ ??? ?????? ?????? ?????? ????.

??? ????? Hypersomnia ????? ?????? ????? ????? sleep apnea ?? ??????? ?????? ???????? ????? ????? ???? ?? ??? ???? ?????? ?? ???? ????? ?????? ?????? Excessive daytime sleepiness ???? ??? ????? ?? ???? ????? ?????? ??? ?? ????? ???? ????? ???????? ????? ??????. ?? ????? ???? ?????? ????? ????? ????????? obstructive sleep apnoea ??? 50% ?? ?????? ?? 40 ?????? ?????? ?????? 1.

???? ??? ?? ????? 1 ???? ??? ????? ??????? ?????? ???? ??? ???????. ???? ????? ??????? ??? ?????? (???????) hypotonia? ?????? ????? clubfoot? ???????? ???????ɡ ????? ?????ѡ???????? ??????. ??? ???? ??? ??????? ?????? ???????.

????? ????????

???? ????? 1 ?? ??? ????? ??????? ?? ?????? ??? ???????? ???????? CTG ?? ??????? ??? ??????? ???? DMPK ??????? ??? ?????? ??????? ?? ?????? 19. ???? ??? ???????? ???????? CTG 5-34 ?? ?????? ???????? ??? ?? ?????? ??????? ?????? ?????? Mutable normal alleles ????? ????? 35-49 ??? ???? ????? ??????? ?????????? ??? ??????? ??????? ???? ????? ??? ????? ???????? ???? ???? ??? ???????? ???? ?? 50 ?? ?????? ?????? ???? ???????? full penetrance alleles ????? ?????? ?? ???? ?????. ???? ??? ???????? ?? ????? ?????? 50-150? ??? ????? ???????? 100-1000? ??? ????? ??????? ???? ?? ???.

????? CNBP (ZNF9) ?? ?????? ???? ???? ?? ?????? ???? ??? ????? ??????? ????? 2? ??? ????? ??? ?????? 3. ????? ???????? 1 ?? ????? CNBP ??????? ????ɡ ?(TG)n(TCTG)n(CCTG). ???? ????? ??? ?????? CCTG ??? ????? ??????? ????? 2. ?????? ??? ?????? CCTG ?? ?????? ??????? ??? 11 ?26? ??? ?? ?????? ??????? ?????? ?????? ????? ????? 27-74? ???? ???? ??? ????????? 75-11000 ?? ?????? ?????? ?????? ????????.?? ???? ??? ??? ????? ???? ?? ????? 2

???????

????? ?? ????? ????? ????? ?? ??? ????? ??????? ?? ??????? ????? ?????? ?? ??? ??????? ?????? ????? ? ??? ?????? ????????? ??????? ???????? CTG ?? ??? DMPK? ???? ???? ?? 34 ?????. ???? ?????????? ???????? ?? ????????? ??????? ????? ?? ?? ???? ?? 100٪ ?? ??????. ??? ???? ????? ?? ????? ?????? ?? ????? ??? ???? ?? 99% ???????? ?????? ??????? ??????? ???????????? polymerase chain reaction (PCR) ?? ???? ?????? Southern blot.

???????

?? ???? ????? ?? ???? ?? ???? ???? ???? ????? ??????? ????? ??? ??????? ??? ????? ??????? ????֡ ???? ??? ???????? ??????? ?????? ?????? ????? ???? 70٪ ?? ????? ??????? ??????? ?? ?????. ?? ???? ???? ???? ???? ?????? ????? ?????? ????? ?????? ?? ???? ??????? ???????. ????? ????? ?????? ????? ???? ?????? ???????? ????????? ????? ?? ????? ????? ??????? ??????? ??????. ?? ???? ???? ?????? ??????? ????? ????? Central sleep apnoea ?? ???? ?????? ????? ????? ????????? ?????? ?????? ????? ?????ѡ ???? ?? ???? ????? ??????? ????????? ????? sleep study. ????? ?? ??? ???????? ???????? ??? ??????? Non-invasive ventilation ??? ??? ???? ??? ?? ??? ??????????. ???? ???? ??? ??????? ??????? ????????? ?modafinil ????? ?????? ?????? ???????.

????????? ???????? ?????? ???? ????? ???????

???? ??? ????? ??????? ?????? ???? ????? ????? ?????. ??? ????? ?????? ???????? ???? ????֠ ?????? 50% ?????? ?????? ??????. ???? ????? ??????? ?? ??? ??????? ????? ??? ????? ????? ??? ????? ??????? ?????? ?????????? ??????? ???????? ?? ??? ????? ??????? ????????.