Identification of a Novel Compound Heterozygous IDUA Mutation Underlies Mucopolysaccharidoses Type I in a Chinese Pedigree

Overview

Journal Mol Genet Genomic Med

Specialty Genetics

Date 2019 Nov 24

PMID 31758674

Citations 2

Authors

Yong-An Zhou

Ping Li

Yanping Zhang

Qiuhong Xiong

Chao Li

Zhonghua Zhao

Yuxian Wang

Han Xiao

Affiliations

Soon will be listed here.

Abstract

Background: Mucopolysaccharidosis type I (MPS I) is a rare autosomal storage disorder resulting from the defective alpha-L-iduronidase (encoded by IDUA) enzyme activity and accumulation of glycosaminoglycans (GAGs) in lysosomes. So far, more than 100 IDUA causative mutations have been identified leading to three MPS I phenotypic subtypes: Hurler syndrome (severe form), Hurler/Scheie syndrome (intermediate form), and Scheie syndrome (mild form).

Methods: Whole-exome sequencing (WES) was performed to identify the underlying genetic mutations. To verify the identified variations, Sanger sequencing was performed for all available family members following PCR amplification. The impact on IDUA protein was analyzed by sequential analysis and homology modeling.

Results: A novel IDUA heterozygous single base insertion (c.1815dupT, p.V606Cfs51 ) and a known missence mutation (c.T1037G, p.L346R) were detected in our patient diagnosed as congenital heart disease with heart valve abnormalities. The novel frameshift mutation results in a complete loss of 48 amino acids in the Ig-like domain and causes the formation of a putative protein product which might affect the IDUA enzyme activity.

Conclusions: A novel compound heterozygous IDUA mutation (c.1815dupT, p.V606Cfs51 ) was found in a Chinese MPS I family. The identification of the mutation facilitated accurate genetic counseling and precise medical intervention for MPS I in China.

Citing Articles

Metabolic Cardiomyopathies and Cardiac Defects in Inherited Disorders of Carbohydrate Metabolism: A Systematic Review.

Conte F, Sam J, Lefeber D, Passier R Int J Mol Sci. 2023; 24(10).

PMID: 37239976 PMC: 10218694. DOI: 10.3390/ijms24108632.

Identification of a novel compound heterozygous IDUA mutation underlies Mucopolysaccharidoses type I in a Chinese pedigree.

Zhou Y, Li P, Zhang Y, Xiong Q, Li C, Zhao Z Mol Genet Genomic Med. 2019; 8(1):e1058.

PMID: 31758674 PMC: 6978265. DOI: 10.1002/mgg3.1058.

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