Abstract：
Split hand/foot malformation (SHFM) is a clinically heterogeneous genetic disorder, which is mainly characterized by median clefts of the hand/feet due to the absence of the central digital rays. Several subgroups of SHFM have been identified, including SHFM1 to SHFM6. SHFM3 is an autosomal dominant disease, which has been identified to associate with a 500 kb microduplication at 10q24. The duplication involved several genes, including LBX1, BTRC, POLL, FBXW4, and so forth. In the study, using trio clinical exome sequencing, a 120 kb microduplication containing only BTRC were identified in a Chinese family affected with SHFM3. Further confirmation was performed using qRT-PCR assay, which showed that the 120 kb duplication was co-segregated with SHFM phenotypes in the family. It is the smallest duplication which has ever been reported relating to SHFM3. Furthermore, the transcription levels of BTRC mRNA in lymphocyte of the proband was significantly higher than that in the healthy control. The study provided evidence for the limb malformation caused by abnormal BTRC expression, and suggested that next generation sequencing could provide more precise diagnosis to SHFM3 patients.
摘要：
手/足分裂畸形（SHFM）是一种临床异质性遗传疾病，由于没有中央数字射线，其主要特征是手/脚的正中裂痕。已经确定了SHFM的几个子组，包括SHFM1到SHFM6。SHFM3是一种常染色体显性疾病，已被确定与10q24处的500kb微重复相关联。复制涉及几个基因，包括LBX1、BTRC、POLL,FBXW4等等。在研究中,使用三重临床外显子组测序，在一个患有SHFM3的中国家庭中发现了仅包含BTRC的120kb微重复。使用qRT-PCR测定进行进一步确认，这表明该家族中120kb的重复与SHFM表型共分离。这是有史以来与SHFM3有关的最小重复。此外，先证者淋巴细胞中BTRCmRNA的转录水平明显高于健康对照组。该研究为BTRC表达异常引起的肢体畸形提供了证据，并表明下一代测序可以为SHFM3患者提供更精确的诊断。
