目的: 探讨先天性并指畸形一大家系的临床特点及其致病基因突变分析，为该类疾病的产前诊断以及携带者筛查提供依据。方法: 通过家系调查，对家系患者进行临床表型分析并进行手和脚部X光检查；绘制系谱图，整理分析家系资料；采集家系成员外周血并提取基因组DNA；通过外显子测序方法筛选候选基因，将捕获的候选基因突变位点进行PCR扩增后Sanger测序验证分析。结果: 该家系已传4代，并指患者共9例，其中男4例，女5例，Ⅰ2、Ⅱ4、Ⅲ5,7,10等5例患者为单侧并指，Ⅲ16和Ⅳ3,6,7等4例患者为双侧手指并指，脚趾均为正常。先证者及其家系患者均为HOXD13基因的第二外显子917位点发生G>A的突变，导致306位氨基酸从精氨酸到谷氨酰胺的改变，即c.917G＞A（P.R306Q）。家系正常成员均无此突变。结论: 该先天性并指家系属于常染色体显性方式遗传，HOXD13，c.917G＞A（p.R306Q）基因突变位点是该并指家系的致病突变。该家系Ⅲ12成员表型正常但致病基因携带者，表明该家系存在不完全外显特点。

Objective: The aim of this study was to investigate the clinical characteristics and analysis the causal geneof a large Mongolian family with congenital syndactyly, to provide the basis for prenatal diagnosis and carrier screening. Method: Through family investigation, clinical phenotype analysis, X-ray photography of hands and feet were carried out in the family patients. Then drew the pedigree, collected and sorted out the family data. Exon sequencing method was adopted to screen candidate genes using genomic DNA from peripheral blood of the family members. At last, PCR the candidate genes, and verified captured candidate genes by Sanger sequencing. Result: This family disease has passed on for 4 generations. There were 9 patients with syndactyly, including 4 males and 5 females. Ⅰ2, Ⅱ4, Ⅲ5,7,10 were unilateral syndactyly, Ⅲ16 and Ⅳ3,6,7 were bilateral syndactyly, and all the toes were normal. The proband and other patients in his family had the G>A mutation in exon 917 of HOXD13 gene, which resulted in the change of 306 amino acid residue from arginine to glutamine, c.917G>A (p. R306Q). The mutation was not found in normal family members. Conclusion: The congenital syndactyly in this family was the autosomal dominant hereditary pattern, and the pathogenic mutation located on HOXD13, c.917G>A (p. R306Q). The phenotype of the carrier Ⅲ12 was normal, indicating that the pathogenic gene had a feature of incomplete dominance.

R764.43

内蒙古自治区个体化用药工程技术研究中心开放课题(MDK2018008)；内蒙古民族大学科学研究项目(NMDYB18076)