分析凝血因子VIII多态性标记物作为巴西甲型血友病家庭携带者检测手段的研究。

Analysis of Factor VIII polymorphic markers as a means for carrier detection in Brazilian families with haemophilia A.

作者信息

de Carvalho F M, de Vargas Wolfgramm E, Paneto G G, de Paula Careta F, Spagnol Perrone A M, de Paula F, Louro I D

机构信息

Departamento de Ciências Biológicas Centro de Ciências Humanas e Naturais Universidade Federal do Espírito Santo, Vitória, Brazil.

出版信息

Haemophilia. 2007 Jul;13(4):409-12. doi: 10.1111/j.1365-2516.2007.01475.x.

DOI:10.1111/j.1365-2516.2007.01475.x

PMID:17610558

Abstract

Haemophilia A is an X-linked, recessively inherited bleeding disorder of varying severity, which results from the deficiency of procoagulant factor VIII f(8). Linkage diagnosis using polymorphic markers in the f8 gene is widely used to detect carriers. The objective of this study was to verify the informativeness of three polymorphic markers in the Brazilian population, to evaluate the usefulness of such markers in carrier detection procedures. Sixty-three unrelated healthy volunteers and 10 haemophilic families were studied. Two microsatellite repeats and one HindIII RFLP markers were used. Carrier and non-carrier status could be determined in 80% of females investigated. Intron 13 markers presented the highest heterozygosity rate (79%) followed by intron 22 (68%) and intron 19 (57%). When all three markers were used together, linkage analysis informativeness increased significantly. We conclude that these markers are suitable for carrier detection in the Brazilian population and we recommend their use in combination to maximize diagnostic efficiency.

摘要

甲型血友病是一种X连锁隐性遗传性出血性疾病，严重程度各异，由促凝血因子VIII（F8）缺乏所致。利用F8基因中的多态性标记进行连锁诊断被广泛用于检测携带者。本研究的目的是验证三种多态性标记在巴西人群中的信息含量，评估这些标记在携带者检测程序中的实用性。研究了63名无亲缘关系的健康志愿者和10个血友病家庭。使用了两个微卫星重复序列和一个HindIII限制性片段长度多态性（RFLP）标记。在所调查的80%女性中能够确定携带者和非携带者状态。内含子13标记的杂合率最高（79%），其次是内含子22（68%）和内含子19（57%）。当同时使用所有三种标记时，连锁分析的信息含量显著增加。我们得出结论，这些标记适用于巴西人群的携带者检测，并且我们建议联合使用它们以最大限度提高诊断效率。