Clinical and genetic analysis of mucolipidosis in 3 pedigrees and literature review / 中华儿科杂志

ABSTRACT

Objective@#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 ML Ⅱα/β, 11 type ML Ⅲ α/β and 4 type ML Ⅲ γ. 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.