Copy Number Variant Sequencing reveals a 10q24.31-q24.32 haploid duplication in a Chinese family with congenital Split hand/foot malformation

Gaoli, Qihui, Fanhongye, Zhangjun, Yinxiaojing, Fengjie

Pediatrics in Henan Province People's Hospital, Zhengzhou City, 450003 China

【Abstract】Objective To identify pathogenic genotype in a chinese family with congenital split hand/foot malformation 3(SHFM3) and understand functions of candidate genes in SHFM3. Method High throughput whole genome sequencing technique and copy number variant sequencing (CNVseq) were performed to determine the copy number variations in affected individuals. Candidate genes were further screened for mutations through sanger sequencing.  Result All 3 affected cases in the family share a potential pathogenic haplotype in the SHFM3 locus.  CNVseq showed a microduplication at chromosome 10q24 spanning 480kb (chr10:102955157-10345157) and covering five genes, FBXW4, LBX1, BTRC, POLL and DPCD, that co-segregated with the SHFM3 phenotypes (OMIM 246560). The CNV analysis showed the microduplication covering the whole gene of FBXW4 and overlapping BTRC exons. No potential pathogenic coding mutations of these genes were found. Conclusion: This study determined the molecular basis of SHFM3 in a Chinese family using high throughput CNVseq, haplotype analysis and sanger sequencing. According to previous studies, our results reveals that FBXW4 may play a key role in limb development.

【Key word】SHFM3; 10q24 microduplication; FBXW4