DCX基因嵌合变异致男性皮质下带状灰质异位1例临床特点及基因变异分析

Clinical features and gene mutation analysis of a male case of subcortical band heterotopia caused by mosaic mutation of DCX gene

目的:探讨DCX基因嵌合变异致男性皮质下带状灰质异位1例的临床表型及基因变异特点。方法:回顾性分析2020年8月郑州大学附属儿童医院神经内科确诊的1例男性皮质下带状灰质异位患者的临床资料、头颅磁共振成像(MRI)影像学特征,同时采用二代测序方法进行家系3人的全外显子测序(trio-WES),并采用聚合酶链反应-Sanger测序对可疑变异进行家系验证,分析其基因变异特点。结果:患儿男性,5岁1个月,因间断抽搐4年6个月入院,头围48 cm,四肢肌张力稍高,智力、运动发育均落后,头颅MRI显示皮质下带状灰质异位,家系全外显子基因检测发现患儿DCX基因存在半合子嵌合变异(嵌合比例44%)c.148A>G(p.k50E),口腔黏膜及尿液分析嵌合比例分别为38.2%和44.8%,父母均为野生型,该变异位点国内外未见报道。结论:DCX基因嵌合变异可致男性皮质下带状灰质异位,DCX基因c.148A>G(p.k50E)变异可能为先证者的病因,该变异扩充了皮质下带状灰质异位基因变异谱。

Objective To investigate the clinical phenotype and genotype of a male case of subcortical band heterotopia caused by mosaic mutation of DCX gene.Methods The clinical data and magnetic resonance imaging(MRI)features of a male case of subcortical band heterotopia diagnosed in the Department of Neurology,Children′s Hospital Affiliated to Zhengzhou University in August 2020 were analyzed retrospectively.At the same time,the whole exon sequencing of the families was performed by next generation sequencing method,the suspicious mutation was verified by polymerase chain reaction Sanger sequencing,and their genetic mutation characteristics were analyzed.Results The proband,one male,aged 5 years and 1 month,was hospitalized in August 2020 with the complaint of intermittent convulsions for 4 years and six months.Clinical features included that limb muscle tension was slightly high,intellectual and motor development was backward,and head circumference was 48 cm.MRI of his head showed diffuse thick subcortical band heterotopia.The detection of whole exon sequencing in his family showed that there was hemizygous mosaic mutation in DCX gene(mosaic ratio 44%),c.148A>G(p.k50E).The mosaic ratios of oral mucosa and urinalysis were 38.2%and 44.8%respectively.His parents were wild-type,The mutation found in this patient has not been reported at home and abroad.Conclusions The mosaic variation of DCX gene can cause subcortical band heterotopia in males.The variation of DCX gene c.148A>G(p.k50E)may be the possible cause of the proband,which expands the variation spectrum of subcortical band heterotopia.