10p末端三体致多发畸形的临床表型及遗传学分析

目的分析1例多发畸形患儿的遗传学原因,探讨其染色体变异与表型的相关性。方法应用常规G显带分析患儿外周血染色体核型,采用低覆盖度全基因组高通量测序技术(low-coverage massively parallel copy number variation sequencing,CNV-seq)进行DNA拷贝数变异分析,并通过荧光原位杂交对患儿及父母进行验证,以判断变异区域的结构变化和遗传学来源。结果G带检测患儿核型为46,XX,3pter+?。CNV-seq分析结果显示患儿10pl3pl5.3区存在约13.5 Mb重复(60466〜13556655)和3p26.3区存在636 kb微缺失(60064〜695821)0对患儿及父母进行FISH验证,明确患儿核型为46,XX,ish der(3)t(3;10)(10p+,3p dim),父母荧光原位杂交验证结果未见异常,提示患儿为新发变异。结论患儿的10pl3pl5.3重复与智力缺陷、生长迟缓、畸形表型、胃食管返流等临床表型相关。3p末端缺失涉及CHL1基因,该基因在大脑的构建和功能中起重要作用,可能同时协作影响患儿的智力发育。

Phenotypic and genetic analysis of a child with multiple malformations due to 10p13p15.3 duplication

Objective To explore the basis for a child with multiple malformations and correlate her genotype w让h phenotype.Methods The child was subjected to G-banding chromosomal analysis first,and low-coverage massively parallel copy number variation sequencing(CNV-seq)was used to define the aberrant region.The results were verified by fluorescence in situ hybridization(FISH).Results The child was found to have a karyotype of 46,XX,3pter+?.CNV-seq has identified a 13.5 Mb duplication at 10p13p15.3(60466-13556655)and a 636 kb microdeletion at 3p26.3(60064-695821).Her karyotype was the refore specified as 46,XX,ish der(3)t(3;10)(10p+,3pdim)by FISH.Both of her parents were normal,which suggested an de novo origin of the above variant.Conclusion The de novo 10pl3pl5.3 duplication probably underlies the mental retardation,development delay,dysmorphism,and gastroesophageal reflux in the child.The CHL1 gene from the 3p26.3 region may play an important role in the formation and function of the brain,which may underlie the intellectual deficit in this child.