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