TRIP12基因c.40C>T杂合变异致智力障碍一例

Intellectual disability due to heterozygous c.40C>T variant of TRIP12 gene in a patient

目的对1例智力障碍患者的TRIP12基因进行变异分析,明确其致病原因。方法应用全外显子测序及Sanger测序验证,并对其家系成员进行验证。结果测序结果显示先证者TRIP12基因存在c.40C>T(p.Arg14X)杂合无义变异,其父母该位点未检测到变异,为新发变异(de novo),查阅人类基因变异数据库未见该变异类型报道。根据美国医学遗传学及基因组学学会遗传变异解读指南,c.40C>T变异判定为致病性变异(PVS1+PS2+PP3)。结论这例患者为TRIP12基因c.40C>T杂合变异导致的常染色体显性遗传智力障碍。

Objective To explore the genetic basis for a patient with intellectual disability.Methods Whole exome sequencing and Sanger sequencing were carried out for the patient.The result was verified in her family.Results DNA sequencing revealed that the patient has carried a heterozygous nonsense c.40C>T(p.Arg14X)variant of the TRIP12 gene,which was de novo in origin.The variant was unrecorded in the Human Gene Mutation Database.Based on the ACMG standards and guidelines,the variant was predicted to be pathogenic(PVS1+PS2+PP3).Conclusion The patient was diagnosed with autosomal dominant intellectual disability due to heterozygous c.40C>T variant of the TRIP12 gene.