肌酸转运载体缺乏一家系临床与遗传学分析

目的报道由SLC6A8基因突变导致肌酸转运载体缺乏(creatine transporter deficiency,CRTR-D)一家系的临床和遗传特点。方法对2018年9月山西省儿童医院神经内科收治的1例全面性发育迟缓伴癫痫患儿及家系进行临床分析与遗传学检查,分析其致病基因突变情况。结果先证者男性,3岁3个月,走路不稳,不会说话,频繁抽搐,尿肌酸/肌酐比值升高,磁共振波谱提示脑肌酸峰值降低。先证者舅舅与患儿症状相似,先证者母亲仅表现出学习困难,先证者父亲、姐姐及外祖父母均无症状。测序发现患儿SLC6A8基因(NM_005629)TTC缺失突变[c.1222_1224del(p.Phe408del)],诊断为X-连锁CRTR-D;患儿母亲及外祖母为杂合突变,患儿舅舅携带同样的半合子突变,先证者父亲、姐姐及外祖父未发现该突变。结论SLC6A8基因突变导致CRTR-D的病例家系中具有相同突变的2名女性携带者临床表现不一,存在表型变异,对研究CRTR-D基因型-表型相关性有重要意义。

Clinical and genetic analysis of a creatine transporter deficiency family

Objective To report the clinical and genetic characteristics of a family of creatine transporter deficiency(CRTR-D)caused by SLC6A8 gene mutation.Methods A patient,who came from Department of Neurology,Shanxi Children′s Hospital in September 2018,with epilepsy and unexplained general developmental retardation,was clinically examined.The medical history of his family was also collected.Genetic detection was performed to analyze their genetic causes.Results The proband,a three years and three months old boy,was walking unsteadily,unable to speak and having frequent seizures,with increased urine creatine/creatinine ratio and decreased peak of cerebral creatine indicated by magnetic resonance spectrum.The proband′s uncle had the similar symptoms with him.The mother of the proband only showed some learning difficulties,while the father,sister and grandparents of the proband had no symptoms.The proband was found to have TTC deletion mutation of SLC6A8 gene(NM_005629),c.1222_1224del(p.Phe408del),suggestting the diagnosis of X-linked CRTR-D.The proband′s mother and grandmother had heterozygous mutations.The proband′s uncle carried the same hemizygous mutation,which was not detected in the proband′s father,sister or grandfather.Conclusion In this family of CRTR-D caused by SLC6A8 gene mutation,two female carriers with the same mutation presented different clinical features,suggesting phenotypic variation,which has a great significance in studying the correlation between genotype and phenotype.