【摘要】 目的 对湖北省一个B1型短指(趾)家系进行基因突变分析。方法 采集家系成员的外周血并提取基因组DNA,对先证者进行全外显子组测序，根据ACMG指南判定位点的致病性，发现疑似致病位点后对家系患者和未受累亲属的该突变位点进行Sanger测序验证。结果 家系中所有患者临床表型符合BDB1的特征，c.2239C>T(p.R747X)这一杂合致病突变在家系中与BDB1共分离。这一突变产生了部分结构域缺失的ROR2截短蛋白，检索人类基因突变数据库(HGMD)、EXAC等多个数据库均未收录，是此前未发现的新的ROR2基因变异位点。进一步对R747及其上下游序列进行保守性分析，发现其在多个物种中高度保守。结论 首次报道B1型短指(趾)ROR2基因c.2239C>T突变，丰富了ROR2基因突变谱，结合我们报道的另一个ROR2终止突变，提示ROR2基因的终止突变可能是湖北省BDB1疾病的主要致病基因突变。更多还原

【Abstract】 Objective To identify the gene mutation of a family with brachydactyly type B1(BDB1) in Hubei Province, China. Methods The samples of peripheral blood from the family members were collected and the genomic DNA was extracted. Whole exome sequencing was performed on the proband and the pathogenicity of the mutation site was determined according to ACMG guidelines. As long as the suspected pathogenic site was found, Sanger sequencing was performed on affected and non-affected relatives in the family. Results The clinical phenotypes of all the patients in this pedigree were consistent with the characteristics of BDB1, and the c.2239 C>T(p.R747 X) heterozygous mutation was co-segregated with BDB1 in the pedigree, which resulted in deletion of partial domain of ROR2 truncated protein. The new mutation in ROR2 gene has not been reported before and was not included in many databases such as Human Gene Mutation Database(HGMD) and EXAC. Further analysis for the conservatism of R747 and its upstream and downstream sequences showed that it was highly conserved in many species. Conclusion c.2239 C>T, a novel mutation of ROR2 gene in the patients with brachydactyly type B1 was firstly reported, which has enriched the mutation spectrum of ROR2 gene. Combined with another ROR2 termination mutation we previously reported, it was indicated that the termination mutation in ROR2 gene might be the main pathogenic mutation in the BDB1 patients found in Hubei Province.更多还原