全外显子组测序发现中国Joubert综合征家系C5orf42基因的新突变

Identification of two novel mutations of C5orf42 in a Chinese family with Joubert syndrome by whole exome sequencing

目的探究一个中国Joubert综合征家系的致病基因及位点。方法对该Joubert综合征家系的先证者进行全外显子组测序,按照ACMG解读规则筛选致病性变异位点,利用聚合酶链式反应(PCR)和Sanger测序进行验证,并在其他家庭成员及192例健康对照者中进行测序验证。结果在先证者的5号染色体的C5orf42基因上存在2个杂合突变位点,分别为c.3676C>T,p.R1226X以及c.8310_8311insT,p.L2770fsX5,这两个位点在家系中符合遗传共分离规律。结论全外显子组测序结合Sanger测序发现C5orf42基因的c.3676C>T,p.R1226X以及c.8310_8311insT,p.L2770fsX5位点为引起该Joubert综合征家系临床病变的突变位点。

Objective：To investigate the genetic mutations in a Chinese family with Joubert syndrome.Methods：Whole exome sequencing was applied to examine the DNA sample of proband patient with Joubert syndrome.Likely pathogenic variants were filtered and selected following the standards and guidelines of the American College of Medical Genetics and Genomics.Polymerase chain reaction followed by Sanger sequencing was used to verify the candidate variants in other family members and healthy controls.Results： Compound heterozygous variants（c.3676 〉C T,p.R1226 X and c.83108311insT,p.L2770fsX5）were identified in C5orf42 and confirmed by co-segregating analysis.Conclusions：Two novel mutations（c.3676〉CT,p.R1226 X c.83108311insT,p.L2770fsX5）of C5orf42 in a Chinese family with Joubert syndrome which broadening the spectrum of C5orf42 mutations were reported.