摘要目的 分析黏脂质累积病(ML)3个家系的临床特征及分子遗传学特点及中国人群ML的临床和基因变异特点.方法 回顾性分析2016年2月—2018年8月在郑州大学第一附属医院遗传与产前诊断中心就诊的3个ML家系患儿的临床资料及家系基因检测结果.应用靶向捕获高通量测序(NGS)技术新生儿遗传代谢病基因panel测序、目的基因Sanger测序,对患儿及其父母进行致病基因检测.以"ML""mucolipidosis,Chinese"检索PubMed数据库及中国知识基础设施工程数据库、万方数据库相关文献,分析总结已报道的中国ML患者基因变异的病例资料.结果 3个家系中患儿起病年龄为(9~90)日龄,共同临床特征为发育迟缓,骨骼多发畸形.3个家系黏脂质累积病致病基因均为GNPTAB基因,共检测到5种基因变异:p.Arg364Ter、p.Ser385Leu、p.Try404Ter、p. Arg587Ter、c.1284+1G>T,其中p.Ser385Leu和c.1284+1G>T为新变异.检索共筛选出8篇文献,共报道26例ML患者,确诊MLⅡα/β型患者11例,MLⅢα/β型患者11例,MLⅢγ型患者4例,c.2715+1G>A和p.Arg364Ter可能是中国人群GNPTAB基因热点变异.结论 ML患者临床主要特征为生长发育迟缓,骨骼异常, NGS结合Sanger测序方法可以高效准确地对ML家系进行基因诊断.GNPTAB基因p.Ser385Leu和c.1284+1G>T为新变异.中国人群GNPTAB基因是ML的主要致病基因,c.2715+1G>A和p.Arg364Ter是GNPTAB基因常见的基因变异位点.

abstractsObjective To investigate the clinical and genetic characteristics of 3 patients with mucolipidosis and to perform literature review. Methods A retrospective analysis was made on the clinical data and genetic test results of 3 pedigrees with mucolipidosis. The patients were followed up at the Genetic and Prenatal Diagnosis Center of the First Affiliated Hospital of Zhengzhou University from February 2016 to August 2018. A neonatal inherited metabolic diseases gene panel including GNPTAB, GNPTG, MCOLN1, etc. was used for next?generation sequencing (NGS) based testing. Sanger sequencing was subsequently used to confirm the suspected pathological variants in the patients and their family members. Original papers on mucolipidosis published up to December 2018 were retrieved from PubMed,CNKI and WanFang databases by using the key words "mucolipidosis" AND "Chinese".Results The onset ages ranged from (9-90) days. The common clinical characteristics of the 3 patients are developmental delay and skeletal abnormalities. Targeted NGS revealed 5 different variations all in GNPTAB including p.Arg364Ter,p.Ser385Leu, p. Try404Ter, p. Arg587Ter, c. 1284+1G>T. Two variants p. Ser385Leu and c. 1284+1G>T were novel. Twenty-six cases of mucolipidosis have been reported in Chinese from 8 papers, which included 11 type MLⅡα/β,11 type MLⅢα/β and 4 type MLⅢγ. c.2715+1G>A and p.Arg364Ter variants are likely the hot variants in Chinese ML patients. Conclusions Mucolipidosis is a rare autosomal recessive disorder characterized by developmental delay and skeletal abnormalities. NGS plus Sanger sequencing detection is effective and accurate for making genetic diagnosis. p.Ser385Leu and c.1284+1G>T of GNPTAB gene are identified as novel pathogenic variants. GNPTAB gene is the main disease causing gene among Chinese ML patients, and c.2715+1G>A and p.Arg364Ter are the most common variants.