CLN6基因复合杂合突变导致神经元蜡样脂褐质沉积症一家系遗传学研究

目的: 探讨一个常染色体隐性遗传神经元蜡样脂褐质沉积症（NCL）家系的遗传学原因。方法: 应用目标区捕获高通量靶向测序对先证者进行候选基因突变筛查，并通过PCR测序在先证者及其父母中对突变位点进行验证；RT-PCR及TA克隆测序考察上述两种突变是否影响剪接。结果: 测序结果显示先证者存在CLN6：c.486+2T>C和c.486+4A>T复合杂合突变，分别来自父母双方。RT-PCR及TA克隆测序提示两种突变均可导致两种异常剪接。结论: CLN6：c.486+2T>C和c.486+4A>T复合杂合突变很可能为该NCL家系患者的遗传学病因，新突变基因丰富了CLN6基因突变谱。

Genetic study of a family of neuronal ceroid lipofuscinosis caused by a heterozygous mutation of CLN6 gene

Objective: To analyze the genetic cause of a family with autosomal recessive neuronal ceroid lipofuscinoses (NCL). Methods: The proband was screened for mutations within the coding region of the candidate genes through high-throughput targeted sequencing. Potential causative mutations were verified by PCR and Sanger sequencing in the proband and his parents. RT-PCR and TA clone sequencing were performed to investigate whether the mRNAs were abnormally spliced. Results: The sequencing results revealed compound heterozygous mutations of CLN6:c.486+2T>C and c.486+4A>T, which were respectively inherited from his parents. RT-PCR and TA cloning sequencing suggested that the mRNAs were abnormally spliced in two forms due to both mutations. Conclusions: The compound heterozygous mutations of CLN6:c.486+2T>C and c.486+4A>T are possibly the genetic causes of the NCL family. Detection of the novel mutation has extended mutation spectrum of CLN6.