Abstract：
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).
CONCLUSIONS: 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.
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).
CONCLUSIONS: 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.
摘要：
目的：探讨1例中性脂质贮积症伴肌病(NLSDM)患儿的临床表型及遗传基础。
方法：选取2021年2月郑州大学第一附属医院收治的肌酸激酶（CK）升高2个月以上患儿作为研究对象。进行了临床和实验室检查，孩子接受了整个外显子组测序。通过她的家庭成员的Sanger测序来验证候选变体。
结果：患者，一个9岁的女性,表现出下肢无力，升高CK水平,和顽固性心肌萎缩症.基因检测显示她藏有c.32C>G（p。S11W）和c.516C>G（p。N172K）PNPLA2基因的复合杂合变体，分别从她的母亲和父亲那里继承。根据美国医学遗传学和基因组学学院（ACMG）的指南，两种变体均被评为可能致病(PM1+PM2_支持+PP3+PP4).
结论：c.32C>G（p。S11W）和c.516C>G（p。PNPLA2基因的N172K）复合杂合变体可能是该儿童重症肌无力和肌酸激酶升高的基础。
方法：选取2021年2月郑州大学第一附属医院收治的肌酸激酶（CK）升高2个月以上患儿作为研究对象。进行了临床和实验室检查，孩子接受了整个外显子组测序。通过她的家庭成员的Sanger测序来验证候选变体。
结果：患者，一个9岁的女性,表现出下肢无力，升高CK水平,和顽固性心肌萎缩症.基因检测显示她藏有c.32C>G（p。S11W）和c.516C>G（p。N172K）PNPLA2基因的复合杂合变体，分别从她的母亲和父亲那里继承。根据美国医学遗传学和基因组学学院（ACMG）的指南，两种变体均被评为可能致病(PM1+PM2_支持+PP3+PP4).
结论：c.32C>G（p。S11W）和c.516C>G（p。PNPLA2基因的N172K）复合杂合变体可能是该儿童重症肌无力和肌酸激酶升高的基础。
