Vin i hc M H Ni Khoa Cng ngh Sinh hc

BNH RI LON NG MUHEMOPHILIA

VIN I HC M H NIKHOA SAU I HC---------------------

GVHD : HVTH :LP :

KT LUNHemophilia APhng php iu trNI DUNGM U

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M U- HEMOPHILIA : l bnh di truyn do thiu ht hay bt thng chc nng ca cc yu t ng mu nh cc yu t VIII, IX, hay XI.- c trng : mu kh ng, d xut huyt, t mu di da, chy mu cc khp....

Bnh hemophilia hay cn gi l bnh ri lon ng mu. y l mt bnh di truyn do thiu ht hay bt thng chc nng ca cc yu t ng mu huyt tng, nh cc yu t VIII, IX hay XI. Bnh c trng bi thi gian ng mu ko di v tng nguy c chy mu; biu hin lm sng ch yu l xut huyt, xut huyt c th t nhin hoc sau chn thng nh. c im xut huyt l m mu bm di da, t mu trong c, chy mu cc khp.

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Ti sao b Hemophilia ?

~ 6000 BN(1996)

- T l mc bnh1/10.000 ngiNm 2020 , ~550.000 BN- Nguyn nhn+ Do di truyn t b m

+ Tuy nhin ~ 30% BN do t bin gen trn NST gii tnh X, sau di truyn cho th h sau.

Hemophilia l bnh tng i him gp. T l mc bnh l 1/10.000 ngi. D on n nm 2020, th gii s c khong 550.000 BN. Ti Vit Nam , theo iu tra nm 1996 c khong 6000 BNC 2 nguyn nhn mc bnh l :Ngi bnh Hemophilia mc bnh t khi sinh ra do nhn gen bnh ca ba m. Tuy nhin khong 30% bnh nhn khng c tin s gia nh. Nhng trng hp ny c cho l do t bin gen bnh thng chuyn thnh gen bnh v gen bnh ny vn di truyn cho th h sau.4

Hemophilia di truyn bng cch no ?Hemophilia l bnh di truyn ln lin quan n gii tnh, gen bnh nm trn nhim sc th gii tnh X.

Cha HemophiliaM khng bnh

Hemophilia l bnh di truyn ln lin quan n gii tnh, gen bnh nm trn nhim sc th X.

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Hemophilia di truyn bng cch no ?Cha khng b bnhM mang gen bnh

Cha HemophiliaM mang gen bnh Hemophilia di truyn bng cch no ?

Hemophilia di truyn bng cch no ?Trng hp ngi m b bnh 100% ngi con trai b bnh v ngi con gi mang gen bnh

3 mc bnh Hemiphilia

Nng yu t ng mu ngi bnh thng l 50% -150%

Bnh thng yu t ng mu c nng t 50 n 150%. Ty thuc nng ny m ngi ta chia hemophilia ra lm 3 mc .9

C nhng loi hemophilia no ?

Thiu ht yu t VIII Hemophilia A( Chim t 80% - 85% )

Suy gim yu t IX Hemophilia B( Chim t 15% - 20% )

Bt thng yu t XI Hemophilia C( Rt t , 1% - 3% )

C 3 loi hemophilia, s gim yu t VIII gy ra bnh hemophilia A, thiu ht yu t IX gy hemophilia B v bt thng yu t XI s gy bnh hemophilia C. Trong hemophilia A chim 80-85%, hemophilia B chim 15-20%, hemophilia C chim t l rt t10

Bnh Hemophilia ABnh hemophilia A l bnh ri lon ng mu di truyn do khim khuyt gen tng hp yu t VIII dn n gim nng hot tnh yu t VIII trong mu

Gen quy nh tng hp FVIII nm v tr Xq28 trn NST gii tnh X.

Gen quy nh tng hp FVIII nm v tr Xq28 trn NST gii tnh X.

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Gen F8 c kch thc 186 kb gm 26 exon trong 24 exon c kch thc t 62 bp - 262 bp v 2 exon ln nht exon 14 (3106 bp) v exon 26 (1958 bp)Bnh Hemophilia A

Gen F8 l mt trong nhng gen ln nht c th, c kch thc 186 kb gm 26 exon trong 24 exon c kch thc t 62 bp - 262 bp v 2 exon ln nht exon 14 (3106 bp) v exon 26 (1958 bp)12

Cc loi t bin trn Gen F8 t bin o on trn NST+ o on intron 22 + o on intron 1

487bp 559bp

DNA ngi bnh thng mu i chng dng (+) khi c khuch i bng phn ng multiplex PCR c 1 bng kch thc tng ng 487 bp. Nu t bin xy ra, khi khuch i s cho 1 on kch thc 559 bp. m bo chnh xc cc vch DNA trn ng l on DNA cn tm, gel c cha on DNA kch thc 559 bp, kch thc 487 bp mu bnh nhn trnh t nucleotid c ct tinh sch ri gii trnh t sau kim tra so snh vi trnh t Genebank. 13

t bin mt on v chn on ln : chim 2-5% BN th nng, c th mt 1 exon hoc mt ton b gen

Cc loi t bin trn Gen F8 Exon 8 v exon 9 khng c vch DNA t bin mt on exon 8 v exon 9

t bin mt on ln chim 2-5% bnh nhn hemophilia A th nng. C th mt 1 exon hoc mt ton b gen. C ch phn t ca dng t bin ny c kt lun l do qu trnh ti t hp do hin tng lp li Alu t bin chn on ln v hin tng Alu lm t gy gen F8 v gy hemophilia A th nngin di sn phm PCR pht hin v tr exon 8, exon 9 ca bnh nhn khng c vch DNA trong khi tt c cc exon cn li u ln vch DNA tng ng vi mu i chng dng. iu ny chng t bnh nhn b t bin mt on exon 8 v exon 9. 14

Cc loi t bin trn Gen F8 t bin im : chim 90 -95% BN th va v nht bin mt 1 on nucleotit

t bim im chim 90- 95% BN th va v nh. Gm c t bin mt 1 on Nu. Kt qu ti exon 4 pht hin thy t bin mt 15 nucleotid ti v tr c.435-450. Khi kim tra s thay i acid amin do t bin gy ra, thy ti v tr protein t 135 n 139 b mt 5 acid amin Tyrosin, Aspartic, Threonin, Valin, Valin (p.135-139delTyrVal). 15

Cc loi t bin trn Gen F8 t bin im : chim 90 -95% BN th va v nht bin sai ngha: thay th nucleotid T thnh nucleotid C

t bin sai ngha: thay th nucleotid T thnh nucleotid C bnh nhn ti exon 14 khi kim tra c t bin ti v tr c.5093 nucleotid T c thay th bng nucleotid C gy ra t bin thay th acid amin Isoleucin bng acid amin Threonin. Nh vy bnh nhn c t bin exon 14 ca gen F8 ti v tr c. 5093T>C (p.Ile927Thr). 16

Cc loi t bin trn Gen F8 t bin im : chim 90 -95% BN th va v nht bin thm nucleotid : t bin thm nucleotid C

t bin thm nucleotid : t bin thm nucleotid CThm mt nucleotid C trn exon 14 ca gen F8. Kim tra trn trnh t Genebank xc nh thay i ny trn exon 14 l c.2777 insC, t bin gy lch khung dch m ton b acid amin cn li t v tr p.927(p.Lys927ins). 17

Cc loi t bin trn Gen F8 t bin im : chim 90 -95% BN th va v nht bin v ngha : t bin to stop codon

t bin v ngha : t bin to stop codont bin thay th nucleotid T bng nucleotid A ti v tr 6425. So snh vi trnh t Genebank cho thy: t bin ny lm thay i acid amin Leucin to thnh stop codon gy dng t ngt qu trnh phin m protein (p.Leu2142Stop).

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Cc loi t bin trn Gen F8 t bin im : chim 90 -95% BN th va v nht bin ti v tr ni

t bin ti v tr ni Vi nhng thay i bt thng gn hoc ti v tr u hoc cui exon l v tr ni gia exon v intronKhi Blast bng phn mm CLC kim tra v tr ni thy bnh nhn HA45 thay i nucleotid G ca GT u tin ca intron nn c k hiu l c.2113+1. 19

T l cc dng t bin khc nhau trn bnh nhn hemophilia A Vit Nam

y l biu phn b T l cc dng t bin pht hin c trn bnh nhn hemophilia A. t bin ch yu l o on intro 22 v B sai ngha chim 38,1% v 23,9%. B v tr ni exon/intron v b mt on ln l him sy ra vi 4,4%20

Phng php iu tr + B sung Huyt tng ti ng lnh + B sung yu t VIII ( ng lnh, c c, ti t hp )+ Liu php gen : Chuyn on DNA m ha on gen FVIII vo c th ngibnh

Phng php iu tr hin nay l + B sung Huyt tng ti ng lnh + B sung yu t VIII ( ng lnh, c c, ti t hp )Tuy nhin cc bin php ny cn gp nhiu hn ch nh B sung Huyt tng nguy c ly nhim cao cc bnh v ng mu cao do cha c tinh sch. c bit cc phng php ny khng cha tr dt im c bnh, m bnh nhn phi b sung lin tc.Hin nay bin php Liu pho gen c nghin cu thng qua qu trnh chuyn on DNA m ha on gen FVIII vo c th ngi bnh. iu tr bnh a chy mu bng liu php gen ha hn nhiu li ch v bnh c gy ra bi khim khuyt gen, c th iu tr bin i mt dng bnh t th nng thnh th nh ca bnh a chy mu. S dng liu php gen c th kch hot ln n 150% hot ng ca FVIII. Vi ngun cung cp lin tc ca cc sn phm gen, liu php gen c th cha khi bnh a chy mu21

Kt lunVi s tin b ca k thut sinh hc phn t, cc nh khoa hc c th phn tch DNA ca ngi bnh xc nh chnh xc cc tn thng gen gy bnh hemophilia A, cng nh kim sot bnh tt hn nh pht hin ngi ph n mang gen bnh v t vn di truyn trc hn nhn, tng hiu qu trong vic phng nga bnh tt ng thi nng cao cht lng chm sc sc khe trong cng ng. Hin nay cc nghin cu thc nghim trn chut v ch chng minh s thnh cng khi s dng liu php gen iu tr . Cc nghin cu thc nghim lm sng ang c tin hnh sm p dng vo vic cha bnh cho ngi.

Cm n qu thy v cc anh ch lng nghe !