血友病家庭中的携带者检测与产前诊断。

Shetty S, Ghosh K, Bhide A, Mohanty D

Institute of Immunohaematology (ICMR), 13 Floor, New Multistoreyed Building, KEM Hospital, Parel, Mumbai 400012, Maharashtra, India.

Natl Med J India. 2001 Mar-Apr;14(2):81-3.

BACKGROUND

Haemophilias are the commonest X-linked disorders affecting approximately 1 in 10,000 male births. Detection of carrier women in families with haemophilia and subsequent antenatal diagnosis of confirmed carriers are important services for these patients and their relatives. Over the last 6 years we performed carrier detection and antenatal diagnosis in families with patients of haemophilia A and B.

METHODS

During the last 6 years, 159 families with haemophilia A and B were analysed for carrier detection by DNA analysis, using various polymorphic markers of factors VIII and IX genes. The polymorphisms used were intron 18 Bcl I, intron 19 Hind III, intron 22 Xbal and DXS52/St14 of the factor VIII gene and intron I Ddel, intron 4 Taql, 3 Hhal and Residue 148 codon Mnll of the factor IX gene. There were 189 probable carriers (whose carrier status was not known) and 99 obligatory carriers (confirmed carriers by family pedigree analysis) from 102 families with haemophilia A. Of the 57 families with haemophilia B analysed, there were 98 probable and 52 obligatory carriers. All the analyses were carried out by polymerase chain reaction. For antenatal diagnosis, prior to polymorphism analysis, the sex of the foetus was detected by Y chromosome-specific amplification.

RESULTS

One hundred and four females were diagnosed as carriers and 63 as non-carriers by the intragenic polymorphic markers in families with haemophilia A. Eighteen women were informative with only the extragenic marker of factor VIII gene. Four women were not informative with any of the markers used. In families with haemophilia B, 37 women were diagnosed as carriers and 34 as non-carriers by the intragenic markers and 34 were informative only with the extragenic markers. Seventeen women were not informative with any of the markers used. Of the 25 antenatal diagnoses performed (20 haemophilia A, 5 haemophilia B) using the same markers as those used in carrier detection, 14 were male foetuses and 11 female as detected by Y chromosome-specific polymerase chain reaction. Eight were affected males and 6 unaffected. Among the females, 5 were carriers and 6 normal.

CONCLUSION

Using the above polymorphic markers of factors VIII and IX genes, a diagnosis could be made in the majority of families.

背景

血友病是最常见的X连锁疾病，在每10000例男性出生中约有1例受影响。在血友病家庭中检测携带者女性，并对确诊的携带者进行产前诊断，对这些患者及其亲属来说是重要的服务。在过去6年里，我们对甲型和乙型血友病患者家庭进行了携带者检测和产前诊断。

方法

在过去6年中，对159个甲型和乙型血友病家庭进行了分析，通过DNA分析，使用因子VIII和IX基因的各种多态性标记来检测携带者。所使用的多态性包括因子VIII基因的内含子18 Bcl I、内含子19 Hind III、内含子22 Xbal和DXS52/St14，以及因子IX基因的内含子I Ddel、内含子4 Taql、3 Hhal和第148密码子Mnll。在102个甲型血友病家庭中有189名可能的携带者（其携带者状态未知）和99名 obligatory携带者（通过家系分析确诊的携带者）。在分析的57个乙型血友病家庭中，有98名可能的携带者和52名 obligatory携带者。所有分析均通过聚合酶链反应进行。对于产前诊断，在进行多态性分析之前，通过Y染色体特异性扩增检测胎儿性别。

结果

在甲型血友病家庭中，通过基因内多态性标记，104名女性被诊断为携带者，63名被诊断为非携带者。18名女性仅通过因子VIII基因的基因外标记提供信息。4名女性对所使用的任何标记均无信息。在乙型血友病家庭中，通过基因内标记，37名女性被诊断为携带者，34名被诊断为非携带者，34名仅通过基因外标记提供信息。17名女性对所使用的任何标记均无信息。在使用与携带者检测相同的标记进行的25次产前诊断中（20例甲型血友病，5例乙型血友病），通过Y染色体特异性聚合酶链反应检测，14例为男性胎儿，11例为女性胎儿。8例为受影响男性，6例未受影响。在女性中，5例为携带者，6例正常。