HEMOGLOBİNOPATİLER

GENETİK HETEROJENİTE

MOLEKÜLER TANI

Prof. Dr. Mehmet Akif ÇÜRÜK

Çukurova Üniversitesi Tıp Fakültesi

Tıbbi Biyokimya Anabilim Dalı

Hemoglobin A Molekülü

HbA Molekülü ve HbS taşıyıcılığı

HbAS (2αβAβS)

HbSS (2α2βS)

HbA (2α2β) %97

HbA2 (2α2) %3

HbS; Beta globin zinciri 6. Glu>Val

Beta talasemi taşıyıcısı

HbA (2α2β)

HbA2 (2α2)

HbA2 <%3.7

MCV<78

Alfa talasemi taşıyıcısı

HbA (2α2β)

HbA2 (2α2)

HbA2 <%3.5

HbH (β4)

Türkiyede Hemoglobinopatilerin Dağılımı

Altay Ç:Turkish J Hematol 2002;19(2),309

Evlilik öncesi tarama yapılan 33 il

Normal insan hemoglobinleri

Embriyonik

Hemoglobinler

Fetal

Hemoglobin

Erişkin

Hemoglobinleri

Hb Gower 1 (ζ2ε2) Hb F (α2γ2) Hb A (α2β2)

Hb Gower 2 (α2ε2 ) Hb A2 (α2δ2)

Hb Portland (ζ2γ2)

Globin zincirlerinin sentezi

Alfa ve beta globin gen kümeleri

11

16

Hb molekülünde alfa ve beta globin

zincir oranı

Hemoglobin Varyantları

Anormal Hemoglobinler Talasemiler

Akdeniz Anemisi

HEMOGLOBİNOPATİLER

α varyantları

Hb Adana

β varyantları

HbS, Hb İstanbul

α-Talasemiler

β-Talasemiler

Orak Hücre Anemisi CVS

Hemoglobinopati çeşitleri

Hemoglobinopati Türü

Hemoglobin Varyantları

Alfa Talasemiler

Beta Talasemiler

Toplam Sayı

Dünya (n) Türkiye (n)

1000< 52

100< 10

200< 43

1300< 105

Hb S 6 GluVal GAG GTG

Hb C 6 GluLys GAG AAG

Hb E 26 GluLys GAG AAG

HbD-Puncap 121 GluGln GAA CAA

HbO-Arab 121 GluLys GAA AAA

HbH 4

Hb Barts 4

Sık görülen Hemoglobin Varyantları

HbS ve HbD Taşıyıcılarına Ait

Hematolojik Veriler Cins/

Yaş

RBC

1012/L

Hb

g/dL

Hct

%

MCV

fL

MCH

Pg

MCHC

g/dL

Hb

Tipi

β-globin

Genotipi

E-6 4.65 13.7 39.1 84.0 23.6 25.3 AS AS

E-40 5.07 14.4 43.0 84.9 28.4 33.4 AS AS

E-34 5.19 14.2 41.4 79.6 27.3 34.3 AS AS

K-33 4.18 10.8 33.6 80.4 25.8 32.0 AS AS

K-25 4.91 12.4 40.6 82.5 25.2 30.6 AS AS

E-32 5.69 14.9 46.0 80.8 26.2 32.4 AD AD

K-19 5.70 13.9 44.7 80.9 29.2 31.5 AD AD

E-27 4.71 14.1 44.5 94.3 29.9 31.7 AD AD

K-28 4.08 11.4 34.4 84.3 27.9 33.1 AD AD

E-28 5.40 15.8 47.1 87.2 28.3 33.6 AD AD

K-28 3.92 11.7 33.3 84.8 29.8 35.2 AD AD

HbE ve HbC Taşıyıcılarına Ait

Hematolojik Veriler

Cins/

Yaş

RBC

1012/L

Hb

g/dL

Hct

%

MCV

fL

MCH

Pg

MCHC

g/dL

Hb

Elektr.

Beta Globin

Genotipi

K-31 4.66 11.0 33.1 71.1 23.7 33.4 AE AE

K-28 3.85 10.0 30.5 79.1 25.9 32.8 AE AE

E-37 5.44 13.8 21.5 76.5 25.3 33.3 AE AE

E-28 4.36 11.0 34.0 77.8 25.1 31.8 AE AE

K-34 4.47 10.7 34.4 77.0 24.0 31.1 AE AE

K-22 6.06 16.5 46.7 77.0 27.2 35.3 AC AC

E-34 5.70 16.1 45.2 77.4 27.6 35.6 AC AC

K-25 5.00 12.9 38.2 76.3 25.9 33.9 AC AC

E-21 5.84 16.6 45.9 78.6 28.4 26.2 AC AC

E-35 5.75 16.3 45.5 79.1 28.3 35.7 AC AC

Ülkemizde görülen Hemoglobin varyantları Hemoglobin Mutation Hemoglobin Mutation

1 O-Podova α30 GluLys 27 Siirt β27 AlaGly

2 Hasharon α47AspuHis 28 Hakkari β31 LeuArg

3 Monthgomery α48LeuArg 29 G-Copenhagen β47 AspAsn

4 Adana α59 GlyAsp 30 Summer Hill β52 AspHis

5 J-Anatolia 61 LysThr 31 Hamadan β56 GlyArg

6 Ube-2 α68 AsnAsp 32 J-Antakya β65 LysMet

7 Q-Iran α75 AspHis 33 City of Hope β69 GlySer

8 Moabit α86 LeuArg 34 J-Iran β77 HisAsp

9 M-Iwate α87 HisTyr 35 Yaizu β79 AspAsn

10 Çapa α94 AspGly 36 G-Szuhu β80 AsnLys

11 Setif α94 AspTyr 37 Pyrgos β83 GlyAsp

12 G-Georgia α 95 ProLeu 38 Istanbul β92 HisGln

13 Bronovo α103 HisLeu 39 N-Baltimore β95 LysGlu

14 Strumica α112 HisArg 40 Köln β98 ValMet

15 J-Meerut α120 AlaGlu 41 D-Punjab β121 GluGln

16 Tyne β5 ProSer 42 O-Arab β121 GluLys

17 S β6 GluVal 43 Beograd β121 GluVal

18 C β6 GluLys 44 Tunis β124ProSer

19 Ankara β10 AlaAsp 45 Sarrebourg β131 GlnArg

20 D-Ouled Rabah β19 AsnLys 46 Brocton β138 AlaPro

21 E-Saskatoon β22 GluLys 47 A2Yialousa D82 AlaSer

22 G-Cousatta β22 GluAla 48 Baskent γ128 AlaThr

23 D-Iran β22 GluGln 49 Lepore-Boston Hybrid

24 E β26 GluLys 50 P-Nilotic Hybrid

25 Knosos β27 AlaSer 51 Costant Spring Elonged chain

26 Volga β27 AlaAsp 52 Antalya Deletion&Insertion

Ülkemizde sık görülen beta talasemi mutasyonları

Mutasyon Mutasyon Türü %

IVSI-110 + (G→A) 40.8

IVSI-6 + (T→C) 10.3

IVSII-1 0 (G→A) 8.0

IVSII-745 + (C→G) 6.2

IVSI-1 0 (G→A) 5.7

Fsc 8 0 (-AA) 4.7

-30 + (T→A) 4.2

Cd 39 0 (C→T) 2.9

Fsc 8/9 0 (+G) 2.6

Cd 44 0 (–C) 1.8

Fsc 5 0 (-CT) 1.2

Cins/

Yaş

RBC

1012/L

Hb

g/dL

Hct

%

MCV

fL

MCH

Pg

MCHC

g/dL

Hb

Tipi

HbA2

%

Beta Globin

Genotipi

K-26 4.5 10 31 67 21 31 AA 4.8 IVSI-110 (G>A)

E-30 6.8 12 42 61 18 30 AA 4.8 IVSI-1 (G>A)

E-31 5.6 11 38 69 21 31 AA 4.7 Cod 39 (C>T)

K-22 5.0 12 36 72 22 31 AA 4.1 IVSI-6 (C>T)

K-24 5.3 11 35 67 21 31 AA 5.8 Fsc 8 (AA)

K-36 5.2 12 37 71 22 31 AA 5.5 -30 (T>A)

K-25 5.2 10 34 66 20 30 AA 6.1 IVS2-1 (G>A)

K-23 5.6 11 37 65 20 30 AA 5.7 IVS2-745 (C>G)

K-28 5.2 11 35 67 21 31 AA 4.0 Fsc5 (-CT)

K-25 4.9 10 33 67 21 31 AA 4.0 Fsc 44 (-C)

E-26 5.3 10 36 68 20 29 AA 4.2 Fsc 74/75 (-C)

E-26 6.8 12 40 60 17 29 AA 3.6 IVSI-5 (G>C)

E-21 6.0 12 41 67 20 30 AA 4.3 Fsc 8/9 (+G)

β-Talasemi Taşıyıcılarına ait Hematolojik Veriler

Ülkemizde görülen beta talasemi mutasyonları

Position Mutation Position Mutations

1 -101 CT 22 IVS-I-110 GA

2 -88 CT 23 IVS-I-116 TG

3 -87 CG 24 IVS-I-130 GA

4 -30 TA 25 IVS-I-130 GC

5 -28 AC 26 FSC-36/37 -T

6 5’-UTR +22 GA 27 Cd 37 GA

7 FSC-5 -CT 28 FSC 37-39 -7 bp

8 FSC-6 -A 29 Cd 39 CT

9 FSC-8 -AA 30 FSC-44 -C

10 FSC-8/9 +G 31 FSC-74/75 -C

11 Cd 15 GA 32 FSC-82/83 -G

12 FSC 22-24 -AAGTTGG 33 IVS-II-1 GA

13 Cd 30 GC 34 IVS-II-654 CT

14 IVS-I-1 GA 35 IVS-II-745 CG

15 IVS-I-1 GC 36 IVS-II-848 CA

16 IVS-I-1 GT 37 IVS-II-849 AG

17 IVS-I-2 TA 38 3'-UTR -13 bp

18 IVS-I-5 GA 39 Poly A AATAAAAATGAA

19 IVS-I-5 GC 40 Poly A AATAAAAATAAG

20 IVS-I-5 GT 41 Poly A AATAAAAACAAA

21 IVS-I-6 TC 42 290 bp Deletion

BETA TALASEMİ GENOTİPLERİ

Allel durumu Fenotip

Sağlam / Normal

Sessiz taşıyıcı +/ -Thal heterozigot

Homozigot +/+ -Thal homozigot

Beta talasemi intermedia IVS1-6/IVS1-6

Ağır Taşıyıcı 0/ -Thal heterozigot

Homozigot 0 /0 -Thal homozigot

BetaTalasemi Major IVS2-1/IVS2-1

Kombine Heterozigot +/0 -Thal çift heterozigot

Beta talasemi intermedia IVS1-6/IVS2-1

Beta talasemi Major IVS1-1/IVS2-1

Alfa globin gen delesyonları

Alfa talasemi genotipleri

DELESYONEL ALFA TALASEMİ

MUTASYONLARI

3.7 Kb α+

4.2 Kb α+

17.4 Kb Med I α0

20.5 Kb α0

26.4 Kb Med II α0

NONDELESYONEL ALFA TALASEMİ

MUTASYONLARI

PA1* AATAAA→AATAAG α+

PA2** AATAAA→AATGAA α+

5NT DEL α+

Hb ADANA α+

Hb KOYA DORA α+

* Arabian Population

** Turkish and Cyprus population

Alfa globin gen mutasyonları

Delesyonel ve nondelesyonel alfa talasemi

taşıyıcıların hematolojik verileri

E: Erkek, K: Kadın, *MED I, **MED II, 5nt: 5 nüleotid delesyonu (-TGAGG),

PA1: AATAAA→AATAAG, PA2: AATAAA→AATGAA

Cins/Yaş RBC

1012/L

Hb

g/dL

Hct

%

MCV

fL

MCH

pg

MCHC

g/dL

Hb

Tipi

Hb A2

%

Alfa talasemi

Genotipi

Erkek n:5 4.82 13.9 44 92.3 28.8 31.2 AA 2.5 αα/αα

Kadın n:7 4.69 13.6 43 93.2 29.0 31.1 AA 2.5 αα/αα

E-12 5.26 12.5 41 77.9 23.8 30.5 AA 2.1 - α(3.7)/αα

K- 22 4.57 11.9 36 80.0 26.0 32.6 AA 3.0 - α(4.2)/αα

K-25 5.25 10.8 35 70.2 21.4 30.4 AA 2.0 --(17.4)/αα

E -14 6.64 12.7 42 63.7 19.1 30.0 AA 1.9 --(20.5)/ αα

K- 43 5.57 10.9 37 67.9 19.6 28.8 AA 2.4 --(26.5)/ αα

E -15 4.47 12.8 38 85.6 28.5 33.3 AA 1.4 αα/α5nt α

E -28 5.22 13.3 46 89.1 25.5 28.6 AA 2.5 αα/ αPA1 α

K-29 5.20 13.4 42 80.9 25.8 31.8 AA 1.9 αα/αPA2 α

ALFA TALASEMİ GENOTİPLERİ

Gen sayısı Fenotip

Sağlam / Normal

Sessiz taşıyıcı (+) - / -thal-2 heterozigot

Homozigot - /- -thal-2 homozigot

Ağır Taşıyıcı (0) - -/ -thal-1 heterozigot

Bart’s - -/ - - -thal-1 homozigot

HbH - -/- -thal-1/-thal-2

Nondelesyonel -talasemi */ Nondelesyonel -thal

HbH * / * Nondel -thal homozigot

HbH - -/ * -thal-1/Non del -thal

HbH - -/ * -thal-1/Non del -thal

* Nokta mutasyonu

HbH Genotipleri ve hematolojik verileri

Cins/Yaş RBC

1012/L

Hb

g/dL

Hct

%

MCV

fL

MCH

pg

MCHC

g/dL

Hb

Tip

Hb A2

% HbH Genotipi

E-16 4.72 8.8 30 64.0 18.7 29.2 AH 1.7 -- (MED I)/-α(3.7)

K-45 4.67 9.1 35 75.0 20.0 26.0 AH 0.5 -- (20.5)/-α(3.7)

K-41 4.71 9.5 34 71.8 20.1 28.0 AH 0.5 -- (20.5)/-α(4.2)

E-29 5.38 10.3 37 69.4 19.2 22.5 AH 1.4 -- (MEDII)/-α(3.7)

E-18 4.06 6.4 24 59.0 16.0 27.0 AH 1.5 -- (MED I)/α5ntα

K-23 3.81 7.8 26 67.0 20.0 30.0 AH 0.8 -- (MED I)/αPA1α

E-22 3.28 7.4 31 96.0 22.0 23.0 AH 1.3 -- (20.5)/ααCD59

K-11 4.87 8.6 30 62.0 18.0 29.0 AH 0.4 -- (MED II)/α5ntα

E-29 4.42 7.8 33 78.0 18.0 24.0 AH 0.8 αPA1α/αPA1α

-Thalassemia

Mutations

IVSI-110

IVSI-1

IVSI-6

IVSI-5

-30

Abnormal

Hemoglobins

HbS,

HbE,

HbD,

HbC

-Thalassemia Mutations

Alpha 3.7 kb del

Alpha 17.4 kb del

Alpha 20.5 kb del

Alpha 26.5 kb del

Alpha 4.2 kb del

GLOBİN GEN KOMBİNASYONLARI

HbSS ve HbS-β-Talasemili hastaların

Hematolojik Verileri

Cins/Yaş RBC

1012/L

Hb

g/dL

Hct

%

MCV

fL

MCH

Pg

MCHC

g/dL

Hb

Tipi

HbF

%

Beta Globin

Genotipi

K-21 2.22 7.4 22.6 102.0 33.6 32.9 SS 0.3 SS

E-15 5.03 10.7 34.3 68.2 21.4 31.3 SS(F) 9.5 SS

E-17 2.76 8.0 24.8 89.8 28.9 32.2 SS 1.1 SS

E-42 6.08 14.0 45.0 73.9 22.9 31.0 SS 1.1 SS

K-7 3.56 11.0 31.5 96.8 30.9 31.9 SS(F) 14.5 SS

E-9 2.67 6.6 22.7 85.0 24.6 28.9 SD 0.9 SD

E-17 5.18 11.7 37.9 73.2 27.7 31.0 SE 2.2 SE

K-17 4.16 8.5 29.5 70.9 20.6 30.7 SS(F) 3.4 S/IVSI-1

K-6 2.99 9.5 28.9 96.4 31.7 32.9 SS 0.9 S/Fsc5

K-23 5.03 10.5 33.0 65.6 20.9 31.8 SF 15.8 S/IVSI-5

E-12 6.10 13.1 39.5 67.6 22.5 37.5 SS 1.7 S/IVSI-6

E-2 4.55 8.8 29.4 64.5 19.4 30.1 SS 2.0 S/IVSI-110

E-20 2.75 6.0 19.4 70.5 21.6 30.7 SF 10.0 S/Cd39

HbDD, HbD-β-Talasemi ve HbE-β-

Talasemili Hastaların Hematolojik Değerleri Cins

/Yaş

RBC

1012/L

Hb

g/dL

Hct

%

MCV

fL

MCH

Pg

MCHC

g/dL

Hb

Tipi

HbF

%

Beta Globin

Genotipi

E-33 4.24 11.4 32.8 77.5 26.8 34.6 DD 0.4 DD

K-27 4.67 11.7 39.2 73.3 25.1 34.2 DD 1.7 DD

K-18 6.06 12.3 39.8 65.5 20.3 30.9 DD 1.4 D/IVSI-1

E-25 5.98 12.2 39.6 66.2 20.4 30.8 DD 2.3 D/Fsc5

K-48 5.34 11.1 33.9 63.4 20.8 32.9 DD 1.1 D/IVSI-110

K-11 5.98 12.1 38.6 64.6 20.3 31.3 DD 1.7 D/IVSI-110

E-1 4.67 8.5 28.1 60.1 18.2 30.4 EE 1.2 E/IVSI-6

E-40 4.26 10.4 35.4 83.2 24.5 29.4 EF 10.0 E/IVSI-110

HbS ile Delesyonel veya Nondelesyonel

Alfa Talasemi Kombinasyonları

Cins/Yaş RBC

1012/L

Hb

g/dL

Hct

%

MCV

fL

MCH

pg

MCHC

g/dL

Hb

Tipi

Hb A2

%

Alfa talasemi

Genotipi

K-30 4.79 14.0 44 92.3 29.2 31.7 AS 3.1 αα/αα

E-33 4.48 13.0 40 90.6 29.0 32.0 AS 3.5 αα/αα

K-7 5.01 13.4 44 88.8 26.7 30.1 AS 3.5 - α(3.7)/αα

K-27 4.63 12.3 40 86.4 26.6 30.7 AS 3.3 - α(4.2)/αα

E-32 6.22 13.7 43 70.2 22.0 31.3 AS 4.0 --(17.4)/αα

K-29 5.20 10.4 33 63.9 20.0 31.3 AS 3.3 --(20.5)/αα

E-14 5.16 11.3 35 69.6 21.9 31.5 AS 3.7 --(26.5)/αα

E-52 5.95 17.8 54 90.9 29.9 32.9 AS 3.3 αα/αPA2 α

K-20 5.70 9.2 31 55.5 16.1 29.0 AS 1.2 --(17.4)/-α(3.7)

E-30 6.09 10.8 36 60.4 17.7 29.3 AS 1.4 --(26.5)/αPA2 α

HPLC ile belirlenen HbA, HbA2 ve HbX

Cins

Yaş

RBC

1012/L

Hb

g/dL

Hct

%

MCV

fL

MCH

Pg

Fe

μg/dL

Ferritin

ng/mL

Hb-X

%

K/58 3.74 8.1 27.4 70.9 21 37 8.0 21.2

K/67 4.61 10.8 30.1 76.1 25 58 118 17.2

E/32 5.37 11.7 37.3 75.6 24 99 206 17.3

E/37 5.24 12.5 37.9 78.2 26 101 247 19.0

Hemoglobin X

Pedigree of the family with Hb Sarrebourg

DNA Dizi analizi ile Hb Sarrebourg (β131 CAG→CGG)

Baba Anne

Kız kardeş Erkek kardeş

Adı

Soyadı

Cins

Yaş

RBC

1012/L

Hb

g/dL

Hct

%

MCV

fL

MCH

Pg

MCHC

g/dL

HbX

%

G.S. K/29 5.32 13.7 44.4 83.5 25.7 30.7 18.9

C.S. E/34 5.61 14.9 47.5 84.7 26.6 31.3 18.9

Y.S. K/9 4.21 13.1 40.3 95.8 31.1 32.4 32.5

M.O.S E/4 5.41 13.3 42.4 78.4 24.6 31.4 18.6

Hemoglobin AX

Adı

Soyadı

RBC

1012/L

Hb

g/dL

Hct

%

MCV

fL

MCH

Pg

MCHC

g/dL

Hb HPLC

Elktr. Mutasyon

A. S. 5.99 15.1 44.6 74.5 25.3 33.9 AE AD AE-

Saskatoon

S.A. 4.28 12.4 36.3 84.9 29.0 34.1 EE DD EE-

Saskatoon

T. B. 4.46 11.0 34.1 76.5 24.7 32.3 AS AE AG-

Coushatta

Z. B. 4.64 12.5 38.2 82.4 26.9 32.7 AS AE AG-

Coushatta

HbE-Saskatoon ve HbG-Coushatta

Hematolojik Veriler

Kan örneği alınır

EDTA*Na2 tüplere konur

Bu kan örneğinden sayım yapılır

Hemoglobin varyant analizi yapılır

Anormal Hb, beta veya alfa talasemi tanısı alır

Bu kandaki lökositlereden DNA izole edilir

PCR ile mutasyon taraması yapılır

Doğum öncesi tanıda CVS de bu mutasyonlar aranır

Taşıyıcıların belirlenmesi

Taşıyıcıların belirlenmesi

Yüksek Basınçlı Sıvı Kromatografisi (HPLC) kullanılmaktadır

Anormal Hemolobinler tanımlanmakta ve miktarları

ölçülmektedir.

HbA2 miktarı ölçülerek talasemi taşıyıcıları belirlenmektedir.

Kan sayımı yapılarak eritrosit indeksleri ile talasemi

taşıyıcılığına kesin tanı konur.

Beta talasemi taşıyıcılarında HbA2>3.7 ve MCV<79 fL

GAG

T

g

a

CVS Alınması

PCR YÖNTEMLERİ

RFLP ARMS sonuçları

Anne Baba CVS CVS KONTROL Anne Baba CVS CVS (+) (-)

AS AS SS SS AA AS SS

Kontrol

Normal

Kontrol

Mutanat

Mutant

Normal

Normal

Cins Hb RBC MCV MCH MCHC HbA2 HbF

Yıl g/dL 1012/L fL pg g/dL % %

Anne 28 13.4 5.2 80.9 25.8 31.8 1.9 0.8

Baba 32 14.6 5.6 78.0 26.0 33.3 2.4 0.6

PolyA mutasyonu taşıyan bir aile

1 GGCGCACGTGGACGACATGCCCAACGCGCTGTCCGCCCTGAGCGACCTGCACGCGCACAAGCTTCGGGTGGACCC

2 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

1 GGTCAACTTCAAGgt gagcggcgggccgggagcgat ct gggt cgaggggcgagat ggcgcct t cct cgcagggca

2 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - t - - - - - - -

1 gaggat cacgcgggt t gcgggaggt gt agcgcaggcggcggct gcgggcct gggccct cggccccact gaccct c

2 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - *******- - - - g- - - - - - - - - - -

1 t t ct ct gcacagCTCCTAAGCCACTGCCTGCTGGTGACCCTGGCCGCCCACCTCCCCGCCGAGTTCACCCCTGCG

2 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

1 GTGCA CGCCTCCCTGGACAAGTTCCTGGCTTCTGTGAGCACCGTGCTGACCTCCAAATACCGTTAAgct ggagcc

2 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

1 t cggt ggccat gct t ct t gcccct t gggcct ccccccagcccct cct cccct t cct gcacccgt acccccgt ggt

2 - - - - - a- - - g- t - c- - c- - - - - ga- - - - - - - - - - aa- g- a- - - - - - - - - - - - - - - - - - - - - - - *c- - t t - c- - - -

1 ct t t gaat aaagt ct gagt gggcggcagcct gt gt gt gcct gagt t t t t t ccct c*agaaacgt gccagc*at gg

2 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - g- - - c- c- - t g- - cc- g- - t - - - - - - a- a- - - -

GTGCA CGCCTCCCTGGACAAGTT CCTGGC

TTCTGTAG ACACCGTGCTGACCT CCAAATA

CCGTTAAgctggagcctcgg tggccatgcttcttgcccctt

gggcctccccccagcccctcctccccttcc tgcacccgtaccccc

PolyA

gtggtctttaataaagtctgagtgggcggcagccgttgtgtg

g g

cctgagtttttt ctgtcccggaatgtgccaacaatgg

Poly A mutasyonu

N M F C V S CNormal Anne Baba CVS Kontrol

A C G T A C G T A C G T

MOTHER FATHER

CVS

G

G

G

T

G

A

G

T

C

T

G

AG

A

A

T

A

A

G

T

T

T

C

T

G

G

T

C

C

Tcvs Anne Baba CVS

Family RBC

1012 /L

Hb

g/dL

Hct

%

MCV

fL

MCH

Pg

Hb

Elect

HbA2

%

Genotype

Mother

Z.K.26

4.5 10.1 31.7 67.2 21.3 AA 4.8 IVS1-110 /N

Father

M.K.28

6.2 12.3 40.4 64.3 19.6 AA 1.7 - -/

20.5 kb

Boy

K.K.6

4.5 9.4 29.0 63.4 20.6 AA 4.2 IVS1-110/

20.5 kb

Girl

D.K.2

5.35 9.5 29.5 55.0 17.8 AA 4.3 IVS1-110 /N

Alfa ve beta talasemi mutasyonunun birlikte olduğu

bir ailenin hematolojik değerleri

Anne β-Thal (IVS1-110) ve Baba -Thal-1 (20.5kb del)

Prenatal Tanı (Üç ayrı aile) Orak hücre anemili anne ve taşıyıcı baba

Family RBC

1012 /L

Hb

g/dL

Hct

%

MCV

fL

MCH

pg

Hb

Elect

HbF

%

Genotype

Mother

27

2.8 9.3 30.7 99.6 33.0 SF 9.0 SS

Father

23

4.6 13.7 43.4 93.1 29.4 AS 1.4 AS

CVS HbSS

Mother

28

2.3 8.4 25.0 107.7 36.3 SF 9.0 SS

Father

30

4.8 13.1 39.0 81.1 27.2 AS 1.0 AS

CVS HbSS

Mother

23

2.3 7.9 24.3 106.1 34.7 SS 1.6 SS

Father

30

4.9 15.0 46.5 93.8 30.1 AS 0.9 AS

CVS HbSS

Family RBC

1012 /L

Hb

g/dL

Hct

%

MCV

fL

MCH

pg

Hb

Elect

HbF

%

Genotype

Mother

21

2.4 8.0 24.3 108.6 32.7 SF 13.0 SS

Father

26

5.0 14.9 43.4 85.8 29.4 AS 2.2 AS

CVS HbSS

Mother

22

2.7 8.8 27.2 99.3 32.0 SF 11.9 SS

Father

27

4.7 13.7 41.3 86.6 28.8 AS 1.4 AS

CVS HbSS

Mother

24

2.6 8.7 25.8 98.1 33.1 SF 15.0 SS

Father

29

5.0 13.9 40.9 81.7 27.8 AS 2.0 AS

CVS HbAS

Prenatal Tanı Orak hücre anemili anne ve taşıyıcı baba

Family RBC

1012 /L

Hb

g/dL

Hct

%

MCV

fL

MCH

Pg

Hb

Elect

HbF

%

Genotype

Mother

23

2.1 7.9 22.7 104.6 36.2 SS 3.9 SS

Father

25

4.8 13.7 39.2 81.4 28.5 AS 1.8 AS

CVS HbSS

Mother

25

1.6 5.6 16.7 99.9 34.4 SS 5.5 SS

Father

27

4.9 13.9 41.3 83.7 28.2 AS 1.3 AS

CVS HbAS

Prenatal Tanı Orak hücre anemili anne ve taşıyıcı baba

Family RBC

1012 /L

Hb

g/dL

Hct

%

MCV

fL

MCH

Pg

Hb

Elect

HbF

%

Genotype

Mother

27

3.0 9.4 28.7 93.0 30.5 SF 14.2 SS

Father

28

6.7 15.7 47.5 70.0 23.1 AE 1.2 AE

CVS HbES

Prenatal Tanı Orak hücre anemili anne ve taşıyıcı baba (HbAE)

Family RBC

1012 /L

Hb

g/dL

Hct

%

MCV

fL

MCH

pg

Hb

Elect

HbF

%

Genotype

Mother

24

4.2 12.4 36.3 84.9 29.0 EE 1.5 HbE-Saskatoon/

HbE-Saskatoon

Father

27

4.6 14.2 41.2 88.3 30.4 AS 1.2 HbAS

CVS HbA/

HbE-Saskatoon

Prenatal Tanı HbEE anne ve taşıyıcı baba HbAS

Family RBC

1012 /L

Hb

g/dL

Hct

%

MCV

fL

MCH

pg

Hb

Elect

HbF

%

Genotype

Mother

26

4.6 11.9 34.8 75.0 25.7 DD 1.8 HbD/ HbD

Father

34

6.0 16.5 46.7 77.0 27.2 AC 1.9 HbAC

CVS HbCD

Mother

28

4.6 11.9 34.8 75.0 25.7 DD 1.8 HbD/ HbD

Father

36

6.0 16.5 46.7 77.0 27.2 AC 1.9 HbAC

CVS HbAD

Prenatal Tanı HbDD anne ve taşıyıcı baba HbAC

Family RBC

1012/L

Hb

g/dL

Hct

%

MCV

fL

MCH

pg

Hb

Elect

HbA2

%

HbF

%

Genotype

Mother

26

3.7 9.0 29.7 78.4 23.9 SS 2.3 19.1 HbS/IVSI-110

Father

27

5.2 10 34 61 20 AA 6.1 1.1 HbA/IVSI-1

CVS HbS/IVSI-1

Mother

23

5.0 10.5 33.0

65.6 20.9 SS 3.2 15.8 HbS/IVSI-5

Father

28

5.2 11.7 43.2 82.4 28.0 AS 2.9 0.8 HbAS

CVS HbA/IVSI-5

Prenatal Tanı HbS--Thal anne ve taşıyıcı baba

Family RBC

1012/L

Hb

g/dL

Hct

%

MCV

fL

MCH

pg

Hb

Elect

HbA2

%

HbF

%

Genotype

Mother

U26

3.6 7.8 24.9 68.7 21.6 SF 3.5 4.5 HbS/IVSI-110

Father

U26

5.0 15.3 47.4 84.2 27.2 AA 1.7 1.0 Normal

CVS HbA/IVSI-110

Prenatal Tanı HbS--Thal anne ve Normal baba

Family RBC

1012 /L

Hb

g/dL

Hct

%

MCV

fL

MCH

pg

Hb

Elect

HbA2

%

HbF

%

Genotype

Mother

T24

3.7 7.4 25.2 66.9 19.6 AF 4.6 49.1 -30/-30

Father

T30

5.6 13.2 43.9 77.7 23.4 AA 6.2 HbA/-30

CVS HbA/-30

Prenatal Tanı -Thal intermedia anne ve taşıyıcı baba

Yeni Mutasyon Türleri

Mutasyon Türü ve yeri

Hb Adana 1 geni

IVS1-117 1 geni

Poly A 2 geni

IVS2-850 geni

Yayınlanan Dergi ve yılı

Am J Hematol 1993

Br J Hematol 1993

Br J Hematol 1992

Hemoglobin 1995

İlginize teşekkür ederim