一个短指家系临床特征调查及其致病基因的定位

Clinical investigation of a family with brachydactyly type A1 and the identification of the disease gene

目的通过对山东省一个A1型短指（brachydactyly type A1，BDA1）家系的临床特征及致病基因分析，确定该病的遗传类型及其发生机制。方法经家系调查及临床检查确定疾病类型；通过致病基因微卫星多态位点进行连锁分析；采用修饰引物产生引入酶切位点的方法来区分突变基因。结果该家系的短指症为A1型，常染色体显性遗传；发病原因为位于染色体2q35—2q36的IHH基因（indian hedgehoggene）发生了G298A（D100N）错义突变。结论中国山东A1型短指家系的发病机理是IHH基因发生了G298A（D100N）错义突变所致。

Objective To determine the inheritance mode and pathogenesis of a family with brachydactyly type A1 in Jining, Shandong province via clinical feature and disease gene analysis. Method Family survey and clinical examinations were performed to determine the inheritance mode; microsatellite polymorphic markers and polymerase chain reaction-restriction fragment length polymorphism（PCR-RFLP） were employed for linkage analysis and mutation screening respectively. Results The brachydactyly type of the family was type A1 （BDA1）, and autosomal dominant inheritance. A missense mutation （G298A） of the indian hedgehog gene （IHH） was identified in the patients of this family. Conclusion A missense mutation G298A of the IHH gene might be the molecular basis for the brachydactyly type A1 in this family from Shandong province.