目的 鉴定一家系两兄妹同患遗传性脑白质病的致病性变异。方法 收集患儿及家系的临床资料。提取患儿两兄妹 及其父母的外周血DNA，先后采用医学外显子、全外显子、全基因组测序进行遗传学分析及Sanger测序验证。结果 两兄妹临床表 现符合佩梅样病。医学外显子测序及全外显子测序均未发现患儿携带致病性变异，全基因组测序发现两兄妹存在GJC2基因（NM020435.3）c.-167A>T（5’UTR）exon1/2同一纯合变异，常染色体隐性遗传，分别来源于其父母。结论 GJC2基因c.-167A>T为本家 系两兄妹同患佩梅样病的致病性变异，全基因组测序能发现5’UTR区这一位点的异常。

Objective To explore the pathogenic variation of hereditary leukoencephalopathy in two siblings of a family. Methods The clinical data of children and their families were collected. The peripheral blood DNA of the two siblings and their parents were extracted and genetic analysis and Sanger sequencing were performed by medical exon, whole exon and whole genome sequencing. Results The clinical manifestations of two siblings were consistent with Pelizaeus-Merzbacher-like disease. No pathogenic mutation was found in both medical exon sequencing and whole exon sequencing. However, whole-genome sequencing revealed that the two siblings had the same homozygous variant of c.- 167 A>T ( 5’UTR) exon 1 / 2 in the GJC 2 gene (NM- 020435 . 3 ), which was inherited in an autosomal recessive manner from their parents. Conclusion The c.-167A>T of GJC2 gene is a pathogenic variant of Pelizaeus-Merzbacher-like disease in two siblings of the family. Whole-genome sequencing can reveal an abnormality at this locus in the 5’UTR region.