SLC35A2基因突变致马凡综合征家系中West综合征患儿1例报告并文献复习

Clinical characteristics analysis of a child with West syndrome caused by SLC35A2 gene mutation in a Marfan syndrome family and literature review

目的鉴定马凡综合征家系中1例West综合征患儿基因致病性突变,为家系遗传咨询提供依据。方法收集患儿及其家系成员的临床资料进行分析。提取患儿及其父母、外祖母、舅舅的外周血DNA,采用医学外显子二代测序加拷贝数变异检测,再进行Sanger测序验证。并复习相关文献。结果女性患儿,10月龄,反复抽搐发作7个月,表现为婴儿痉挛。患儿及其母亲、外祖母存在马凡综合征体征。患儿及其母亲、外祖母存在FBN1基因c.7240C>T(p.R2414*)无义突变;患儿还存在SLC35A2基因c.601delG(p.A201Qfs*148)移码突变,其父母SLC35A2基因未见该变异,该基因变异既往未见报道。患儿行室间隔修补术,并予托吡酯、半乳糖治疗后癫痫及发育情况好转。检索到临床资料齐全的相关SLC35A2基因突变报道16篇共74例患者,涉及58个位点,其中错义突变最常见,患者可有不同的临床表型,以早期婴儿癫痫性脑病最常见。结论SLC35A2基因c.601delG(p.A201Qfs*148)是马凡综合征家系中该患儿罹患West综合征的致病性变异。该研究扩大了基因突变谱,为该家系的遗传咨询提供了基础;半乳糖联合托吡酯治疗有助于控制癫痫发作和改善发育情况。

Objective To explore the pathogenic gene mutation of a child with West syndrome in a Marfan syndrome family,and to provide the basis for genetic consultation.Methods The clinical data of the child and her family members were collected and analyzed.Peripheral blood DNA of the child and her parents,maternal grandmother and uncle were extracted.The whole exome next genetic sequencing was employed and copy number variation was detected,and then the result was verified by Sanger sequencing.The relevant literature was reviewed.Results A 10-month-old girl had recurrent convulsions for 7 months,presenting as infantile spasm.There were signs of Marfan syndrome in the child,her mother and grandmother.There was nonsense mutation of c.7240C>T(p.R2414*)in FBN1 gene in the proband,her mother and the maternal grandmother.Furthermore,a frameshift mutation of c.601delG(p.A201Qfs*148)in SLC35A2 gene was also found in the proband,but no such mutation was found in SLC35A2 gene of the parents.This gene mutation has not been reported before.The thoracic ventricular septal defect repair was performed for the child.After the treatment with topiramate and galactose supplementation,the epilepsy and development of the child were improved.A total of 16 articles on SLC35A2 gene mutation with complete clinical data were retrieved,involving a total of 74 patients and 58 mutation loci,among which missense mutation was the most common.Patients could have different clinical phenotypes,and early infant epileptic encephalopathy was the most common.Conclusions The SLC35A2 gene c.601delG(p.A201Qfs*148)is a pathogenic variant of West syndrome in Marfan syndrome family.This study expanded the gene mutation spectrum and provided the basis for genetic counseling of the family.Galactose combined with topiramate treatment is helpful to control seizures and improve development.