Cao Lihua, Chen Chen, Leng Yunji, Yan Lulu, Wang Shusen, Zhang Xue, Luo Yang
The Research Center for Medical Genomics, Key Laboratory of Cell Biology,Ministry of Public Health, Key Laboratory of Medical Cell Biology,Ministry of Education, China Medical University, Shenyang, 110122, People's Republic of China.
J Genet. 2017 Sep;96(4):647-652. doi: 10.1007/s12041-017-0810-y.
Hand-foot-genital syndrome (HFGS) is a rare autosomal dominant inherited syndrome characterized by limb malformations and urogenital defects. HFGS is caused by mutations in the HOXA13 gene. The aim of this study was to identify causative mutations in individuals and to explore the molecular pathogenesis in a Chinese family with HFGS. We performed Sanger sequencing and identified a recurrent missense mutation in the homeodomain (c.1123G>T, p.V375F) of HOXA13, molecular modelling predicted the mutation would affect DNA binding, and a luciferase reporter assay indicated that it impaired the ability of HOXA13 to activate transcription of the human EPHA7 promoter. This is the first report of the molecular basis for HFGS caused by missense mutations of HOXA13.
手足生殖器综合征（HFGS）是一种罕见的常染色体显性遗传综合征，其特征为肢体畸形和泌尿生殖系统缺陷。HFGS由HOXA13基因突变引起。本研究的目的是鉴定个体中的致病突变，并探讨一个患有HFGS的中国家系的分子发病机制。我们进行了桑格测序，在HOXA13的同源结构域中鉴定出一个反复出现的错义突变（c.1123G>T，p.V375F），分子建模预测该突变会影响DNA结合，荧光素酶报告基因检测表明它损害了HOXA13激活人EPHA7启动子转录的能力。这是关于HOXA13错义突变导致HFGS的分子基础的首次报道。
