Detailed pedigree analyses and prenatal diagnosis for a family with mucopolysaccharidosis type II

Chuan Zhang,Yan Wang,Xue Chen,Xing Wang,Zongfu Cao,Zhaoyan Meng,Feng Xuan,Bingbo Zhou,Xinqi Wu,Lei Zheng,Ling Hui,Shengju Hao,Furong Zheng,Qinghua Zhang

doi:10.1186/s12920-021-01027-5

Abstract

BackgroundMucopolysaccharidosis type II (MPS II) is an X-linked multisystem disorder caused by mutations in the gene encoding iduronate 2-sulfatase (IDS). The clinical manifestations of MPS II include skeletal deformities, airway obstruction, cardiomyopathy, and neurologic deterioration. MPS II has high genetic heterogeneity disorder, and ~ 658 variants of IDS have been reported.MethodsWe undertook a detailed pedigree analysis of four patients within the same family by targeted next-generation sequencing and Sanger sequencing.ResultsWe identified a novel heterozygous frameshift variant, c.1224delC(p.Pro408ProfsTer31), of IDS in three patients. We defined c.1224delC as a pathogenic variant according to the 2015 guidelines set by the American College of Medical Genetics and Genomics.ConclusionWe reported the second Chinese female MPS II patient. We helped to ensure that these two families had healthy babies. Our findings have enlarged the mutational spectrum of IDS, and these findings could be useful for genetic counseling and the prenatal diagnosis of MPS II.

Highlights

Mucopolysaccharidosis II (MPS II; Online Mendelian Inheritance in Man number (OMIM#): 309900) is a rare X-linked recessive disorder
Mucopolysaccharidosis type II (MPS II) leads to progressive accumulation of glycosaminoglycans in most cell types, tissues, and organs
II9 died at 32 years of age owing to cardiorespiratory disease

Summary

Introduction

Mucopolysaccharidosis II (MPS II; Online Mendelian Inheritance in Man number (OMIM#): 309900) is a rare X-linked recessive disorder. The clinical symptoms of MPS II vary. MPS II can be divided into two main forms: “attenuated” and “severe” [2, 3]. The attenuated form of MPS II often has a slow progression of symptoms [2]. Progressive cognitive deterioration or neurologic involvement are the main factors that determine the severity of MPS II, and ~ 75% of patients have the severe type [3,4,5]. Mucopolysaccharidosis type II (MPS II) is an X-linked multisystem disorder caused by mutations in the gene encoding iduronate 2-sulfatase (IDS). The clinical manifestations of MPS II include skeletal deformities, airway obstruction, cardiomyopathy, and neurologic deterioration. MPS II has high genetic heterogeneity disorder, and ~ 658 variants of IDS have been reported

Methods

Results

Conclusion