一个中国人手足裂畸形基因组拷贝数变异分析

Analysis of genomic copy number variation for a Chinese patient with split hand/split foot malformation

目的探讨单核苷酸多态性（single nucleotide polymorphism, SNP）芯片技术检测到的微小基因组拷贝数变异（copy number variants，CNVs）在诊断手足裂畸形和分子分型中的应用，为该手足裂畸形患者的遗传咨询和产前诊断提供理论依据。方法应用SNP芯片技术对1例疑诊手足裂畸形患者行全基因组拷贝数扫描分析，对于检测到的微小基因组拷贝数变异应用实时荧光定量PCR技术进行验证。结果SNP芯片检测结果发现患者10q24．31—24．32（102955122—103348688，0．39Mb）区域微小重复，包含LBXl、BTRC、POLL相关致病基因。对于检测到的重复区域内的相关致病基因和重复区域紧邻的FBXW4基因，应用实时荧光定量PCR技术验证，结果显示LBXl、BTRC、POLL基因重复，与芯片结果符合，此外检测到与上述重复基因紧邻的FBxw4基因第9外显子重复。结论SNP芯片可快速检出微小CNVs（〈1.0Mb）变异，结合实时荧光定量PCR技术共同验证，为临床产前诊断提供有价值的信息。

Objective To employ single nucleotide polymorphisms （SNP） microarray to detect copy number variations （CNVs） for the diagnosis of disease and molecular classification. Methods For a patient with split-hand/split-foot malformation, genome-wide copy number variants SNP microarray was applied. Tiny copy number variations were verified by real-time fluorescent quantitative PCR. Results The results of SNP microarray has revealed that the patient has carried a 0. 39 Mb duplication in 10q24. 31-24. 32 （102 955 122-103 348 688）, which has encompassed genes including LBX1, BTRC and POLL. By real-time fluorescent quantitative PCR, duplicate area encompassing the pathogenic genes have been verified. The results for LBX1, BTRC, POLL genes were all consistent with the SNP microarray test. Moreover, a duplication was detected in exon 9 of FBXW4 gene which is in nearby. Conclusion SNP chips can efficiently identify tiny CNVs （〈1.0 Mb）. In combination with real-time fluorescence quantitative PCR, this may provide valuable information for prenatal diagnosis.