一个手足裂畸形家系致病基因位点的鉴定

Identification of pathogenic mutation in a Chinese pedigree affected with split hand/split foot malformation

目的对1个中国手足裂畸形家系进行致病基因突变分析。方法应用单核苷酸多态性微阵列(single nucleotide polymorphism array,SNP array)技术对手足裂畸形家系行全基因组拷贝数扫描分析,并对检测到的突变位点应用实时荧光定量PCR进行验证。结果该家系3代成员中共3例患者,均为典型的手足裂畸形,符合常染色体显性遗传。SNP array检测提示患者10q24.31-q24.32(102993649~103333271,0.34Mb)区域微小重复,包含BTCR和DPCD基因。实时荧光定量PCR对致病基因的拷贝数进行验证,结果显示BTRC基因重复,重复在此家系中与疾病共分离。结论10q24.31-q24.32区域微小重复突变可能是该家系的致病原因,基因组微小重复可能致常染色体显性遗传病。

Objective To detect potential mutation in a Chinese pedigree affected with split hand/split foot malformation (SHFM).Methods The patients were screened for genome-wide copy number variations with single nucleotide polymorphism (SNP)microarray.Copy number variations were verified by real-time fluorescence quantitative PCR.Results There were 3 SHFM patients from three generations,which conformed to an autosomal dominant inheritance.SNP microarray assay revealed that all patients have carried a 0.34 Mb duplication in 10q24.31-q24.32 (102993649-103333271)encompassing the BTRC and DPCD genes.The result was verified by real-time fluorescence quantitative PCR,confirming that the duplication has co-segregated with the SHFM phenotype in the pedigree.Conclusion The 10q24.31-q24.32 duplication probably underlies the pathogenesis of SHFM in this pedigree.Tiny copy number variations can result in diseases featuring autosomal dominant inheritance.