hemoglobİnopatİler - tphd.org.tr .Ülkemizde görülen hemoglobin varyantları hemoglobin mutation

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  • HEMOGLOBNOPATLER

    GENETK HETEROJENTE

    MOLEKLER TANI

    Prof. Dr. Mehmet Akif RK

    ukurova niversitesi Tp Fakltesi

    Tbbi Biyokimya Anabilim Dal

  • Hemoglobin A Molekl

  • HbA Molekl ve HbS taycl

    HbAS (2AS)

    HbSS (22S)

    HbA (22) %97

    HbA2 (22) %3

    HbS; Beta globin zinciri 6. Glu>Val

  • Beta talasemi taycs

    HbA (22)

    HbA2 (22)

    HbA2

  • Alfa talasemi taycs

    HbA (22)

    HbA2 (22)

    HbA2

  • Trkiyede Hemoglobinopatilerin Dalm

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

  • Evlilik ncesi tarama yaplan 33 il

  • Normal insan hemoglobinleri

    Embriyonik

    Hemoglobinler

    Fetal

    Hemoglobin

    Erikin

    Hemoglobinleri

    Hb Gower 1 (22) Hb F (22) Hb A (22)

    Hb Gower 2 (22 ) Hb A2 (22)

    Hb Portland (22)

  • Globin zincirlerinin sentezi

  • Alfa ve beta globin gen kmeleri

    11

    16

  • Hb moleklnde alfa ve beta globin

    zincir oran

  • Hemoglobin Varyantlar

    Anormal Hemoglobinler Talasemiler

    Akdeniz Anemisi

    HEMOGLOBNOPATLER

    varyantlar

    Hb Adana

    varyantlar

    HbS, Hb stanbul

    -Talasemiler

    -Talasemiler

    Orak Hcre Anemisi CVS

  • Hemoglobinopati eitleri

    Hemoglobinopati Tr

    Hemoglobin Varyantlar

    Alfa Talasemiler

    Beta Talasemiler

    Toplam Say

    Dnya (n) Trkiye (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

    Sk grlen Hemoglobin Varyantlar

  • HbS ve HbD Tayclarna Ait

    Hematolojik Veriler Cins/

    Ya

    RBC

    1012/L

    Hb

    g/dL

    Hct

    %

    MCV

    fL

    MCH

    Pg

    MCHC

    g/dL

    Hb

    Tipi

    -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 Tayclarna Ait

    Hematolojik Veriler

    Cins/

    Ya

    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

  • lkemizde grlen Hemoglobin varyantlar Hemoglobin Mutation Hemoglobin Mutation

    1 O-Podova 30 GluLys 27 Siirt 27 AlaGly

    2 Hasharon 47AspuHis 28 Hakkari 31 LeuArg

    3 Monthgomery 48LeuArg 29 G-Copenhagen 47 AspAsn

    4 Adana 59 GlyAsp 30 Summer Hill 52 AspHis

    5 J-Anatolia 61 LysThr 31 Hamadan 56 GlyArg

    6 Ube-2 68 AsnAsp 32 J-Antakya 65 LysMet

    7 Q-Iran 75 AspHis 33 City of Hope 69 GlySer

    8 Moabit 86 LeuArg 34 J-Iran 77 HisAsp

    9 M-Iwate 87 HisTyr 35 Yaizu 79 AspAsn

    10 apa 94 AspGly 36 G-Szuhu 80 AsnLys

    11 Setif 94 AspTyr 37 Pyrgos 83 GlyAsp

    12 G-Georgia 95 ProLeu 38 Istanbul 92 HisGln

    13 Bronovo 103 HisLeu 39 N-Baltimore 95 LysGlu

    14 Strumica 112 HisArg 40 Kln 98 ValMet

    15 J-Meerut 120 AlaGlu 41 D-Punjab 121 GluGln

    16 Tyne 5 ProSer 42 O-Arab 121 GluLys

    17 S 6 GluVal 43 Beograd 121 GluVal

    18 C 6 GluLys 44 Tunis 124ProSer

    19 Ankara 10 AlaAsp 45 Sarrebourg 131 GlnArg

    20 D-Ouled Rabah 19 AsnLys 46 Brocton 138 AlaPro

    21 E-Saskatoon 22 GluLys 47 A2Yialousa D82 AlaSer

    22 G-Cousatta 22 GluAla 48 Baskent 128 AlaThr

    23 D-Iran 22 GluGln 49 Lepore-Boston Hybrid

    24 E 26 GluLys 50 P-Nilotic Hybrid

    25 Knosos 27 AlaSer 51 Costant Spring Elonged chain

    26 Volga 27 AlaAsp 52 Antalya Deletion&Insertion

  • lkemizde sk grlen beta talasemi mutasyonlar

    Mutasyon Mutasyon Tr %

    IVSI-110 + (GA) 40.8

    IVSI-6 + (TC) 10.3

    IVSII-1 0 (GA) 8.0

    IVSII-745 + (CG) 6.2

    IVSI-1 0 (GA) 5.7

    Fsc 8 0 (-AA) 4.7

    -30 + (TA) 4.2

    Cd 39 0 (CT) 2.9

    Fsc 8/9 0 (+G) 2.6

    Cd 44 0 (C) 1.8

    Fsc 5 0 (-CT) 1.2

  • Cins/

    Ya

    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)

    -Talasemi Tayclarna ait Hematolojik Veriler

  • lkemizde grlen beta talasemi mutasyonlar

    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 TALASEM GENOTPLER

    Allel durumu Fenotip

    Salam / Normal

    Sessiz tayc +/ -Thal heterozigot

    Homozigot +/+ -Thal homozigot

    Beta talasemi intermedia IVS1-6/IVS1-6

    Ar Tayc 0/ -Thal heterozigot

    Homozigot 0 /0 -Thal homozigot

    BetaTalasemi Major IVS2-1/IVS2-1

    Kombine Heterozigot +/0 -Thal ift heterozigot

    Beta talasemi intermedia IVS1-6/IVS2-1

    Beta talasemi Major IVS1-1/IVS2-1

  • Alfa globin gen delesyonlar

  • Alfa talasemi genotipleri

  • DELESYONEL ALFA TALASEM

    MUTASYONLARI

    3.7 Kb +

    4.2 Kb +

    17.4 Kb Med I 0

    20.5 Kb 0

    26.4 Kb Med II 0

    NONDELESYONEL ALFA TALASEM

    MUTASYONLARI

    PA1* AATAAAAATAAG +

    PA2** AATAAAAATGAA +

    5NT DEL +

    Hb ADANA +

    Hb KOYA DORA +

    * Arabian Population

    ** Turkish and Cyprus population

    Alfa globin gen mutasyonlar

  • Delesyonel ve nondelesyonel alfa talasemi

    tayclarn hematolojik verileri

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

    PA1: AATAAAAATAAG, PA2: AATAAAAATGAA

    Cins/Ya 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 /

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

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

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

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

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

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

    E -15 4.47 12.8 38 85.6 28.5 33.3 AA 1.4 /5nt

    E -28 5.22 13.3 46 89.1 25.5 28.6 AA 2.5 / PA1

    K-29 5.20 13.4 42 80.9 25.8 31.8 AA 1.9 /PA2

  • ALFA TALASEM GENOTPLER

    Gen says Fenotip

    Salam / Normal

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

    Homozigot - /- -thal-2 homozigot

    Ar Tayc (0) - -/ -thal-1 heterozigot

    Barts - -/ - - -thal-1 homozigot

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

    Nondelesyonel -talasemi */ Nondelesyonel -thal

    HbH * / *