Thalassemia Prevention : Screening and Prenatal Diagnostic Approaches

Thalassemia Prevention: ScreeningandPrenatal DiagnosticApproaches DistanceLearningCourse FromResearchtopractice:Trainingcoursein Sexual...
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Thalassemia Prevention: ScreeningandPrenatal DiagnosticApproaches DistanceLearningCourse FromResearchtopractice:Trainingcoursein SexualandReproductiveHealthResearch CommunityGenetics Marina Kleanthous Molecular Genetics Thalassaemia Department The Cyprus Institute of Neurology & Genetics

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Thalassaemia ƒ Thispresentationincludes: ƒ ƒ ƒ ƒ

Introduction Thalassaemiacontrolprograms Strategyforthepreventionofthedisease Prenataldiagnosticapproaches

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Haemoglobinopathies ƒ Structureofglobin chain ƒ Rateofsynthesisofglobin chains (Thalassaemias) ƒ HereditaryPersistenceofFetalHaemoglobin (HPFH)

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Haemoglobinopathies ȽǦthalassaemia Thalassaemias (350) ȾǦthalassaemia

Hb S AbnormalHaemoglobins (887)

Hb D Hb E 4

Thalassaemia ƒ Reduction or absence of one of the globin polypeptidesmakinguphaemoglobin ƒ Haemoglobinisatetramercomposedof2ȽǦ typeglobin chainsand2ȾǦtypeglobin chains

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HumanHaemoglobins andGlobin Genes ƒ Thalassaemias arehereditaryblooddisorderscausedbya reducedsynthesisofoneormoreoftheglobin chains Chrom. 16 ȗ

ȥȗ

ȥĮ2 ȥĮ1 Į2

Chrom. 11 Į1

ș1

İ

GȖ ǹȖ

Į 2 İ2 Į2 Ȗ2 ȗ2 Ȗ2 ȗ2 İ2 (Gower - I) (Portland) (Gower-II) (Hb-F) Embryo

Fetus

ȥȕ

Į2 ȕ2 (Hb-ǹ)

į

ȕ

Į2 į2 (Hb-ǹ2)

Adult

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Haematopoiesis Embryonic haemoglobins Gower-I ȗ2İ2 Gower-II

Į2İ2

Portland

Ȗ2ȗ2

Foetal Haemoglobin Hb-F

Į2Ȗ2

Adult haemoglobin Hb-A

Į2ȕ2

Hb-A2

Į2į2

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ȾǦthalassaemia >200ȾǦglobin genemutations CommonȾǦglobin genemutations

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ȾǦthalassaemia ƒ Globin chainimbalance ƒ AccumulationofexcessȽǦglobin chainsin erythroid precursors(ineffective erythropoiesis)andRBC(haemolytic anaemia)

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CommonDeletional andnonǦDeletional ȽǦThalassaemiaMutations LJ

Inter LJHVR

ǙLJ Ǚǂ2

Ǚǂ1

ǂ2

ǂ1

lj

Inter HVR

-ǂ3.7 - -MEDI - -MEDII -ǂ20.5

Nondeletional ȽǦthal mutations ǂ2 IVSI Donor site GA[GGTGA]GG ǂ2 Poly(A) signal AATAAA

GAGG…….(5nt deletion)

AATGAA

(PA-2) 10

WorldDistributionofHaemoglobinopathies ƒ One of the most common inherited blood disorder in the world ƒ 250 million people (4.5%) are carriers of a potentially pathologic gene ƒ 300, 000 infants are born with a major haemoglobinopathy 11

Thalassaemia ƒ ƒ ƒ ƒ ƒ ƒ

Severeanaemia Regularbloodtransfusion Ironchelation therapy Bonemarrowtransplantation(BMT) Genetherapy Drugtherapy

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Thalassaemiacontrolprograms ƒ NationalprogramǦ effectivestrategy ƒ Infrastructure ƒ PatientTreatment ƒ Preventionofthedisease

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Thalassaemiacontrolprograms NationalProgram–– EffectiveStrategy ƒ HelpfromWHOandTIFandexpertsinthefield ƒ Extendoftheproblem ƒ Communitypriorities ƒ Economicsituation ƒ Distribution ƒ Ethical(therapeuticabortionoption) ƒ Nationalfinancialsupportoftheprogram 14

Thalassaemiacontrolprograms Infrastructure–– ThalassaemiaCenter ƒ Clinics ƒ Haematology Lab ƒ MolecularBiology Lab

Peripheral Center

Peripheral Center

Sc re e La nin C b g Reference Center

ic n li

Peripheral Center

Molecular Biology Peripheral Center

Peripheral Center Peripheral Center

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Thalassaemiacontrolprograms Prevention ƒ Publiceducation ƒ Carrierscreening ƒ Geneticcounseling ƒ PrenatalDiagnosis

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PreventionPrograms ƒ Euro Mediterranean countries (Italy, Greece, Cyprus) ƒ Middle East countries (Iran 1997) ƒ SE-Asia countries (Asian Network for the control of thalassaemia was established on 2004)

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PreventionPrograms Publiceducation ƒ Schools ƒ Leaflets ƒ Media ƒ Conferences/Seminars ƒ Professionals ƒ ToinformNOTtostigmatize

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PreventionPrograms CarrierScreening ƒ Populationscreening ƒ Highriskgroups ƒ Pregnantwomen

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CarrierDetection ƒ Haematology ƒ Hbs electrophoresis ƒ Biosynthesis

NORMAL MCH (pgt) >27 HbA2(%) 27 HbA2(%)

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