HEMOGLOBİNOPATİLER GENETİK HETEROJENİTE MOLEKÜLER TANI Prof. Dr. Mehmet Akif ÇÜRÜK Çukurova Üniversitesi Tıp Fakültesi Tıbbi Biyokimya Anabilim Dalı
Hemoglobin A Molekülü
A Molekülü ve S taşıyıcılığı A (2α2β) 97 A2 (2α2 )3 AS (2αβAβS) SS (2α2βS) S; Beta globin zinciri 6. Glu>Val
Beta talasemi taşıyıcısı A (2α2β) A2 (2α2 ) A2 <3.7 MCV<78
Alfa talasemi taşıyıcısı A (2α2β) A2 (2α2 ) A2 <3.5 H (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 Gower 1 (ζ 2 ε 2 ) F (α 2 γ 2 ) A (α 2 β 2 ) Gower 2 (α 2 ε 2 ) A 2 (α 2 δ 2 ) Portland (ζ 2 γ 2 )
Globin zincirlerinin sentezi
Alfa ve beta globin gen kümeleri 11 16
molekülünde alfa ve beta globin zincir oranı
HEMOGLOBİNOPATİLER Hemoglobin Varyantları Anormal Hemoglobinler Talasemiler Akdeniz Anemisi α varyantları Adana β varyantları S, İstanbul α-talasemiler β-talasemiler Orak Hücre Anemisi CVS
Hemoglobinopati çeşitleri Hemoglobinopati Türü Dünya (n) Türkiye (n) Hemoglobin Varyantları 1000< 52 Alfa Talasemiler 100< 10 Beta Talasemiler 200< 43 Toplam Sayı 1300< 105
Sık görülen Hemoglobin Varyantları S 6 Glu Val GAG GTG C 6 Glu Lys GAG AAG E 26 Glu Lys GAG AAG D-Puncap 121 Glu Gln GAA CAA O-Arab 121 Glu Lys GAA AAA H 4 Barts 4
S ve D Taşıyıcılarına Ait Hematolojik Veriler Cins/ Yaş RBC 10 12 /L g/dl Hct MCV fl MCH Pg MCHC g/dl 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
E ve C Taşıyıcılarına Ait Hematolojik Veriler Cins/ Yaş RBC 10 12 /L g/dl Hct MCV fl MCH Pg MCHC g/dl 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 Glu Lys 27 Siirt β27 Ala Gly 2 Hasharon α47aspu His 28 Hakkari β31 Leu Arg 3 Monthgomery α48leu Arg 29 G-Copenhagen β47 Asp Asn 4 Adana α59 Gly Asp 30 Summer Hill β52 Asp His 5 J-Anatolia 61 Lys Thr 31 Hamadan β56 Gly Arg 6 Ube-2 α68 Asn Asp 32 J-Antakya β65 Lys Met 7 Q-Iran α75 Asp His 33 City of Hope β69 Gly Ser 8 Moabit α86 Leu Arg 34 J-Iran β77 His Asp 9 M-Iwate α87 His Tyr 35 Yaizu β79 Asp Asn 10 Çapa α94 Asp Gly 36 G-Szuhu β80 Asn Lys 11 Setif α94 Asp Tyr 37 Pyrgos β83 Gly Asp 12 G-Georgia α 95 Pro Leu 38 Istanbul β92 His Gln 13 Bronovo α103 His Leu 39 N-Baltimore β95 Lys Glu 14 Strumica α112 His Arg 40 Köln β98 Val Met 15 J-Meerut α120 Ala Glu 41 D-Punjab β121 Glu Gln 16 Tyne β5 Pro Ser 42 O-Arab β121 Glu Lys 17 S β6 Glu Val 43 Beograd β121 Glu Val 18 C β6 Glu Lys 44 Tunis β124pro Ser 19 Ankara β10 Ala Asp 45 Sarrebourg β131 Gln Arg 20 D-Ouled Rabah β19 Asn Lys 46 Brocton β138 Ala Pro 21 E-Saskatoon β22 Glu Lys 47 A2Yialousa D82 Ala Ser 22 G-Cousatta β22 Glu Ala 48 Baskent γ128 Ala Thr 23 D-Iran β22 Glu Gln 49 Lepore-Boston Hybrid 24 E β26 Glu Lys 50 P-Nilotic Hybrid 25 Knosos β27 Ala Ser 51 Costant Spring Elonged chain 26 Volga β27 Ala Asp 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
β-talasemi Taşıyıcılarına ait Hematolojik Veriler Cins/ Yaş RBC 10 12 /L g/dl Hct MCV fl MCH Pg MCHC g/dl Tipi A 2 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)
Ülkemizde görülen beta talasemi mutasyonları Position Mutation Position Mutations 1-101 C T 22 IVS-I-110 G A 2-88 C T 23 IVS-I-116 T G 3-87 C G 24 IVS-I-130 G A 4-30 T A 25 IVS-I-130 G C 5-28 A C 26 FSC-36/37 -T 6 5 -UTR +22 G A 27 Cd 37 G A 7 FSC-5 -CT 28 FSC 37-39 -7 bp 8 FSC-6 -A 29 Cd 39 C T 9 FSC-8 -AA 30 FSC-44 -C 10 FSC-8/9 +G 31 FSC-74/75 -C 11 Cd 15 G A 32 FSC-82/83 -G 12 FSC 22-24 -AAGTTGG 33 IVS-II-1 G A 13 Cd 30 G C 34 IVS-II-654 C T 14 IVS-I-1 G A 35 IVS-II-745 C G 15 IVS-I-1 G C 36 IVS-II-848 C A 16 IVS-I-1 G T 37 IVS-II-849 A G 17 IVS-I-2 T A 38 3'-UTR -13 bp 18 IVS-I-5 G A 39 Poly A AATAAA AATGAA 19 IVS-I-5 G C 40 Poly A AATAAA AATAAG 20 IVS-I-5 G T 41 Poly A AATAAA AACAAA 21 IVS-I-6 T C 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
Alfa globin gen mutasyonları DELESYONEL ALFA TALASEMİ MUTASYONLARI NONDELESYONEL ALFA TALASEMİ MUTASYONLARI 3.7 Kb α + 4.2 Kb α + 17.4 Kb Med I α 0 20.5 Kb α 0 26.4 Kb Med II α 0 PA1 * AATAAA AATAAG α + PA2 ** AATAAA AATGAA α + 5NT DEL α + ADANA α + KOYA DORA α + * Arabian Population ** Turkish and Cyprus population
Delesyonel ve nondelesyonel alfa talasemi taşıyıcıların hematolojik verileri Cins/Yaş RBC 10 12 /L g/dl Hct MCV fl MCH pg MCHC g/dl Tipi A 2 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/α 5nt α E -28 5.22 13.3 46 89.1 25.5 28.6 AA 2.5 αα/ α PA1 α K-29 5.20 13.4 42 80.9 25.8 31.8 AA 1.9 αα/α PA2 α E: Erkek, K: Kadın, *MED I, **MED II, 5nt: 5 nüleotid delesyonu (-TGAGG), PA1: AATAAA AATAAG, PA2: AATAAA AATGAA
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 H - -/- -thal-1/ -thal-2 Nondelesyonel -talasemi * / Nondelesyonel -thal H * / * Nondel -thal homozigot H - -/ * -thal-1/non del -thal H - -/ * -thal-1/non del -thal * Nokta mutasyonu
H Genotipleri ve hematolojik verileri Cins/Yaş RBC 10 12 /L g/dl Hct MCV fl MCH pg MCHC g/dl Tip A 2 H 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)/α 5nt α K-23 3.81 7.8 26 67.0 20.0 30.0 AH 0.8 -- (MED I)/α PA1 α E-22 3.28 7.4 31 96.0 22.0 23.0 AH 1.3 -- (20.5)/αα CD59 K-11 4.87 8.6 30 62.0 18.0 29.0 AH 0.4 -- (MED II)/α 5nt α E-29 4.42 7.8 33 78.0 18.0 24.0 AH 0.8 α PA1 α/α PA1 α
GLOBİN GEN KOMBİNASYONLARI Abnormal Hemoglobins S, E, D, C -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 -Thalassemia Mutations IVSI-110 IVSI-1 IVSI-6 IVSI-5-30
Cins/Yaş SS ve S-β-Talasemili hastaların Hematolojik Verileri RBC 10 12 /L g/dl Hct MCV fl MCH Pg MCHC g/dl Tipi F 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
DD, D-β-Talasemi ve E-β- Talasemili Hastaların Hematolojik Değerleri Cins /Yaş RBC 10 12 /L g/dl Hct MCV fl MCH Pg MCHC g/dl Tipi F 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
S ile Delesyonel veya Nondelesyonel Alfa Talasemi Kombinasyonları Cins/Yaş RBC 10 12 /L g/dl Hct MCV fl MCH pg MCHC g/dl Tipi A 2 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/α PA2 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)/α PA2 α
HPLC ile belirlenen A, A2 ve X
Hemoglobin X Cins Yaş RBC 10 12 /L g/dl Hct MCV fl MCH Pg Fe μg/dl Ferritin ng/ml -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
Pedigree of the family with Sarrebourg
DNA Dizi analizi ile Sarrebourg (β131 CAG CGG)
Baba Anne
Kız kardeş Erkek kardeş
Hemoglobin AX Adı Soyadı Cins Yaş RBC 10 12 /L g/dl Hct MCV fl MCH Pg MCHC g/dl X 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
E-Saskatoon ve G-Coushatta Hematolojik Veriler Adı Soyadı RBC 10 12 /L g/dl Hct MCV fl MCH Pg MCHC g/dl HPLC Elktr. Mutasyon A. S. 5.99 15.1 44.6 74.5 25.3 33.9 AE AD S.A. 4.28 12.4 36.3 84.9 29.0 34.1 EE DD T. B. 4.46 11.0 34.1 76.5 24.7 32.3 AS AE Z. B. 4.64 12.5 38.2 82.4 26.9 32.7 AS AE AE- Saskatoon EE- Saskatoon AG- Coushatta AG- Coushatta
Taşıyıcıların belirlenmesi Kan örneği alınır EDTA*Na2 tüplere konur Bu kan örneğinden sayım yapılır Hemoglobin varyant analizi yapılır Anormal, 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 Yüksek Basınçlı Sıvı Kromatografisi (HPLC) kullanılmaktadır Anormal Hemolobinler tanımlanmakta ve miktarları ölçülmektedir. A2 miktarı ölçülerek talasemi taşıyıcıları belirlenmektedir. Kan sayımı yapılarak eritrosit indeksleri ile talasemi taşıyıcılığına kesin tanı konur. Beta talasemi taşıyıcılarında A2>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 (+) (-) Kontrol Mutant Normal Normal Normal AS AS SS SS AA AS SS Kontrol Mutanat
PolyA mutasyonu taşıyan bir aile Cins RBC MCV MCH MCHC A 2 F Yıl g/dl 10 12 /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
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 c t c t gc a c a gctcctaagccactgcctgctggtgaccctggccgcccacctccccgccgagttcacccctgcg 2 --------------------------------------------------------------------------- 1 GTGCA CGCCTCCCTGGACAAGTTCCTGGCTTCTGTGAGCACCGTGCTGACCTCCAAATACCGTTAAgc t gga gc c 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--tt-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--tg--cc-g--t------a-a----
Poly A mutasyonu GTGCA CGCCTCCCTGGACAAGTT CCTGGC TTCTGTAG ACACCGTGCTGACCT CCAAATA CCGTTAAgctggagcctcgg tggccatgcttcttgcccctt gggcctccccccagcccctcctccccttcc tgcacccgtaccccc PolyA gtggtctttaataaagtctgagtgggcggcagccgttgtgtg g g cctgagtttttt ctgtcccggaatgtgccaacaatgg
Normal N Anne M Baba F CVS CVS Kontrol C
A C G T A C G T A C G T MOTHER FATHER G G G T G A G T C T G A G A A T A A G T T T C T G G T C C T cvs Anne Baba CVS
Alfa ve beta talasemi mutasyonunun birlikte olduğu bir ailenin hematolojik değerleri Family RBC 10 12 /L g/dl Hct MCV fl MCH Pg Elect A 2 Genotype Mother Z.K.26 Father M.K.28 4.5 10.1 31.7 67.2 21.3 AA 4.8 IVS1-110 /N 6.2 12.3 40.4 64.3 19.6 AA 1.7 --/ 20.5 kb Boy K.K.6 Girl D.K.2 4.5 9.4 29.0 63.4 20.6 AA 4.2 IVS1-110/ 20.5 kb 5.35 9.5 29.5 55.0 17.8 AA 4.3 IVS1-110 /N 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 Hct MCV MCH F Genotype 10 12 /L g/dl fl pg Elect Mother 27 Father 23 CVS Mother 28 Father 30 CVS Mother 23 Father 30 CVS 2.8 9.3 30.7 99.6 33.0 SF 9.0 SS 4.6 13.7 43.4 93.1 29.4 AS 1.4 AS SS 2.3 8.4 25.0 107.7 36.3 SF 9.0 SS 4.8 13.1 39.0 81.1 27.2 AS 1.0 AS SS 2.3 7.9 24.3 106.1 34.7 SS 1.6 SS 4.9 15.0 46.5 93.8 30.1 AS 0.9 AS SS
Prenatal Tanı Orak hücre anemili anne ve taşıyıcı baba Family RBC Hct MCV MCH F Genotype 10 12 /L g/dl fl pg Elect Mother 21 Father 26 CVS Mother 22 Father 27 CVS Mother 24 Father 29 CVS 2.4 8.0 24.3 108.6 32.7 SF 13.0 SS 5.0 14.9 43.4 85.8 29.4 AS 2.2 AS SS 2.7 8.8 27.2 99.3 32.0 SF 11.9 SS 4.7 13.7 41.3 86.6 28.8 AS 1.4 AS SS 2.6 8.7 25.8 98.1 33.1 SF 15.0 SS 5.0 13.9 40.9 81.7 27.8 AS 2.0 AS AS
Prenatal Tanı Orak hücre anemili anne ve taşıyıcı baba Family RBC Hct MCV MCH F Genotype 10 12 /L g/dl fl Pg Elect Mother 23 Father 25 CVS Mother 25 Father 27 CVS 2.1 7.9 22.7 104.6 36.2 SS 3.9 SS 4.8 13.7 39.2 81.4 28.5 AS 1.8 AS SS 1.6 5.6 16.7 99.9 34.4 SS 5.5 SS 4.9 13.9 41.3 83.7 28.2 AS 1.3 AS AS
Prenatal Tanı Orak hücre anemili anne ve taşıyıcı baba (AE) Family RBC Hct MCV MCH F Genotype 10 12 /L g/dl fl Pg Elect Mother 27 Father 28 CVS 3.0 9.4 28.7 93.0 30.5 SF 14.2 SS 6.7 15.7 47.5 70.0 23.1 AE 1.2 AE ES
Prenatal Tanı EE anne ve taşıyıcı baba AS Family RBC Hct MCV MCH F Genotype 10 12 /L g/dl fl pg Elect Mother 24 Father 27 CVS 4.2 12.4 36.3 84.9 29.0 EE 1.5 E-Saskatoon/ E-Saskatoon 4.6 14.2 41.2 88.3 30.4 AS 1.2 AS A/ E-Saskatoon
Prenatal Tanı DD anne ve taşıyıcı baba AC Family RBC Hct MCV MCH F Genotype 10 12 /L g/dl fl pg Elect Mother 26 Father 34 CVS Mother 28 Father 36 CVS 4.6 11.9 34.8 75.0 25.7 DD 1.8 D/ D 6.0 16.5 46.7 77.0 27.2 AC 1.9 AC CD 4.6 11.9 34.8 75.0 25.7 DD 1.8 D/ D 6.0 16.5 46.7 77.0 27.2 AC 1.9 AC AD
Prenatal Tanı S- -Thal anne ve taşıyıcı baba Family RBC 10 12 /L g/dl Hct MCV fl MCH pg Elect A 2 F Genotype Mother 26 Father 27 CVS 3.7 9.0 29.7 78.4 23.9 SS 2.3 19.1 S/IVSI-110 5.2 10 34 61 20 AA 6.1 1.1 A/IVSI-1 S/IVSI-1 Mother 23 Father 28 CVS 5.0 10.5 33.0 65.6 20.9 SS 3.2 15.8 S/IVSI-5 5.2 11.7 43.2 82.4 28.0 AS 2.9 0.8 AS A/IVSI-5
Prenatal Tanı S- -Thal anne ve Normal baba Family RBC 10 12 /L g/dl Hct MCV fl MCH pg Elect A 2 F Genotype Mother U26 Father U26 CVS 3.6 7.8 24.9 68.7 21.6 SF 3.5 4.5 S/IVSI-110 5.0 15.3 47.4 84.2 27.2 AA 1.7 1.0 Normal A/IVSI-110
Prenatal Tanı -Thal intermedia anne ve taşıyıcı baba Family RBC 10 12 /L g/dl Hct MCV fl MCH pg Elect A 2 F Genotype Mother T24 Father T30 CVS 3.7 7.4 25.2 66.9 19.6 AF 4.6 49.1-30/-30 5.6 13.2 43.9 77.7 23.4 AA 6.2 A/-30 A/-30
Yeni Mutasyon Türleri Mutasyon Türü ve yeri Yayınlanan Dergi ve yılı Adana 1 geni Am J Hematol 1993 IVS1-117 1 geni Br J Hematol 1993 Poly A 2 geni Br J Hematol 1992 IVS2-850 geni Hemoglobin 1995
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