一个短指症E2型伴肥胖症家系的致病基因鉴定及遗传学分析

Mutation analysis of a pedigree affected with brachydactyly type E2 and obesity

目的鉴定1个短指症伴肥胖症家系的致病基因,为遗传咨询和产前诊断提供依据。方法先证者为郑州大学附属儿童医院内分泌遗传代谢科收治的1例临床和X线片初诊为短指症E2型伴肥胖症患儿,应用外显子捕获结合二代测序技术对先证者致病基因筛查,采用Sanger测序方法对家系进行验证和遗传分析。结果先证者PTHLH基因第1外显子发现c.125A>C错义突变,导致谷氨酰胺变为脯氨酸(p.Gln42Pro)。该杂合突变在人类基因突变数据库未见报道,SIFT (0)和PolyPhen (0.999)程序评估其可能有害。Sanger测序结果与二代测序结果一致,证实先证者的c.125A>C杂合突变来自其母亲,其舅舅和妹妹也携带相同杂合突变,但其父亲该位点无突变。结论PTHLH基因c.125A>C错义突变可能是该家系致病突变位点。

Objective To identify pathogenic mutation in a pedigree affected with brachydactyly and obesity. Methods Peripheral blood sample was collected for extraction of genomic DNA. Exons capture combined with next generation sequencing (NGS) was carried out to identify potential mutation. Sanger sequencing was used to verify the results. Results NGS has identified a novel heterozygous missense mutation (c.125A>C, p. Gln42Pro) in the exon 1 of PTHLH gene. The result was verified by Sanger sequencing. The mutations was derived from his mother. His uncle and sister have also carried the same heterozygous mutation. Conclusion A novel mutation of the PTHLH gene has been identified in a pedigree affected with brachydactyly type E2 and obesity.