一个染色体14q微缺失的遗传学分析

目的分析1例自闭症、智力低下和癫痫患儿的遗传学病因。方法应用常规G显带染色体核型分析、单核昔酸多态性微阵列(single nucleotide polymorphism array,SNP array)技术检测染色体变异,用高通量测序筛选致病变异位点,Sanger测序验证,查阅数据库及文献分析,以明确缺失区及致病变异基因的病理意义。结果患儿及其父母外周血G显带核型分析结果均未见异常。SNP array检测发现患儿染色体14 qll.2区存在460 kb的缺失,高通量及Sanger测序显示患儿携带NALCN基因新发变异,患儿及其母亲COL4A5基因发生半合子变异。结论染色体14qll.2微缺失与NALCN变异可能与患儿自闭症、智力低下及癫痫等表型相关。

Genetic analysis of a case of chromosome 14q microdeletion

Objective To explore the genetic etiology of a child with autism,mental retardation and epilepsy.Methods Conventional G-banding chromosomal analysis was carried out.Chromosomal variation was also detected by single nucleotide polymorphism microarray(SNP array).Pathogenic mutations were screened by high-throughput sequencing and validated by Sanger sequencing.Pathologic significance of the candidate mutations was analyzed through search of database and literature review.Results No karyotypic abnormality was found with the child and his parents,while SNP array has detected a 460kb deletion in the 14qll.2 region in the child.High-throughput and Sanger sequencing revealed a novel mutation of the NALCN gene in the child,in addition with a hemizygous mutation of the COL4A5 gene in the child and his mother.Conclusion The 14q11.2 microdeletion and NALCN mutation may contribute to the autism,mental retardation and epilepsy in this child.