ATRX新致病性变异致X连锁智力低下家系分析

The family of ATR-X syndrome caused by the novel mutation in ATRX gene

目的:分析一个α地中海贫血X连锁智力障碍(ATR-X)综合征家系的致病基因突变。方法:对该ATR-X综合征家系先证者进行全外显子组测序,通过生物信息学分析筛选候选的致病基因突变位点,利用聚合酶链反应(PCR)和Sanger测序验证该家族成员的致病突变位点。结果:全外显子组测序发现先证者的X染色体ATRX基因存在半合子变异(c.161;62del,p.Ser54Ter),家系成员Sanger测序结果表明该变异在家系中符合遗传共分离规律。结论:ATRX基因c.161;62del变异为引起该家系ATR-X综合征的遗传学因素。

Objective:To investigate the pathogenic genetic mutation of a family with ATR-X syndrome.Methods:Whole exome sequencing was performed on the proband of the family with ATR-X syndrome.The candidate pathogenic variants were screened by bioinformatics analysis.Polymerase chain reaction(PCR)and Sanger sequencing were used to verify the pathogenic genetic mutation site of the family members.Results:Whole exome sequencing revealed a novel hemizygous variation(c.161;62 del,p.Ser54 Ter)of ATRX gene on X chromosome of the proband.The verification of family members by Sanger sequencing showed that the variation was conformed to the co-segregation in the family.Conclusion:The novel mutation(c.161;62 del)of ATRX gene is the genetic factor causing ATR-X syndrome in this family.