中性脂肪沉积症伴肌病患儿1例的临床特征及遗传学分析

Clinical characteristics and genetic analysis of a child with Neutral lipid storage disease with myopathy

目的探讨1例中性脂肪沉积症伴肌病(NLSDM)患儿的临床表型以及基因变异。方法选择2021年2月因"发现高肌酸激酶(CK)升高2月余"就诊于郑州大学第一附属医院的1例NLSDM患儿作为研究对象,对其进行临床和实验室检查,并应用全外显子组测序进行基因变异分析,对候选变异进行Sanger测序家系验证。结果患儿为9岁女性,表现为双下肢乏力、持续CK增高且营养心肌治疗无效。基因检测提示患儿PNPLA2基因存在母源性c.32C>G(p.S11W)和父源性c.516C>G(p.N172K)复合杂合变异。根据美国美国医学遗传学与基因组学学会相关指南,上述变异均被评级为可能致病性变异(PM1+PM2_Supporting+PP3+PP4)。结论PNPLA2基因c.32C>G(p.S11W)和c.516C>G(p.N172K)复合杂合变异考虑为该患儿肌无力和CK增高的遗传学病因。

Objective To explore the clinical phenotype and genetic basis of a child with Neutral lipid storage disease with myopathy(NLSDM).Methods A child who was admitted to the First Affiliated Hospital of Zhengzhou University in February 2021 for a history of elevated creatine kinase(CK)for over 2 months was selected as the study subject.Clinical and laboratory examinations were carried out,and the child was subjected to whole exome sequencing.Candidate variants were validated by Sanger sequencing of her family members.Results The patient,a 9-year-old female,had exhibited weakness in the lower limbs,elevated CK level,and refractory cardiomyotrophy.Genetic testing revealed that she has harbored c.32C>G(p.S11W)and c.516C>G(p.N172K)compound heterozygous variants of the PNPLA2 gene,which were respectively inherited from her mother and father.Based on the guidelines from the American College of Medical Genetics and Genomics(ACMG),both variants were rated as likely pathogenic(PM1+PM2_Supporting+PP3+PP4).Conclusion The c.32C>G(p.S11W)and c.516C>G(p.N172K)compound heterozygous variants of the PNPLA2 gene probably underlay the myasthenia gravis and elevated creatine kinase in this child.