Clinical Genetics
Genetic analysis of a Chinese pedigree affected with Mucopolysaccharidosis type ⅢA
Zuo Hanheng, Li Yinping, Cui Yinghua, Zhang Jinguo, Shen Caiyun, Zhu Wenya, Du Chunlei
Published 2023-04-10
Cite as Chin J Med Genet, 2023, 40(4): 452-457. DOI: 10.3760/cma.j.cn511374-20221107-00766
Abstract
ObjectiveTo explore the clinical and genetic characteristics of a patient with hypertrophic cardiomyopathy as the initial manifestation of Mucopolysaccharidosis type Ⅲ A(MPS ⅢA).
MethodsA female patient with MPS Ⅲ A who was admitted to the Affiliated Hospital of Jining Medical University in January 2022 and her family members (seven individuals from three generations) were selected as the study subjects. Clinical data of the proband were collected. Peripheral blood samples of the proband was collected and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing. Heparan-N-sulfatase activity was determined for the disease associated with the variant site.
ResultsThe proband was a 49-year-old woman, for whom cardiac MRI has revealed significant thickening (up to 20 mm) of left ventricular wall and delayed gadolinium enhancement at the apical myocardium. Genetic testing revealed that she has harbored compound heterozygous variants in exon 17 of the SGSH gene, namely c. 545G>A (p.Arg182His) and c. 703G>A (p.Asp235Asn). Based on guidelines from the American College of Medical Genetics and Genomics(ACMG), both variants were predicted to be pathogenic (PM2_Supporting + PM3+ PP1Strong+ PP3+ PP4; PS3+ PM1+ PM2_Supporting + PM3+ PP3+ PP4). Sanger sequencing confirmed that her mother was heterozygous for the c. 545G>A (p.Arg182His) variant, whilst her father, sisters and her son were heterozygous for the c. 703G>A (p.Asp235Asn) variant. Determination of blood leukocyte heparan-N-sulfatase activity suggested that the patient had a low level of 1.6 nmol/(g·h), whilst that of her father, elder and younger sisters and son were all in the normal range.
ConclusionThe compound heterozygous variants of the SGSH gene probably underlay the MPS ⅢA in this patient, for which hypertrophic cardiomyopathy is an associated phenotype.
Key words:
Mucopolysaccharidosis Ⅲ; SGSH gene; Whole exome sequencing; Hypertrophic cardiomyopathy; Pedigree
Contributor Information
Zuo Hanheng
Department of Cardiology, the Affiliated Hospital of Jining Medical University, Shandong Provincial Key Laboratory for the Diagnosis and Treatment of Cardiac Diseases, Jining, Shandong 272029, China
Li Yinping
Department of Cardiology, the Affiliated Hospital of Jining Medical University, Shandong Provincial Key Laboratory for the Diagnosis and Treatment of Cardiac Diseases, Jining, Shandong 272029, China
Cui Yinghua
Department of Cardiology, the Affiliated Hospital of Jining Medical University, Shandong Provincial Key Laboratory for the Diagnosis and Treatment of Cardiac Diseases, Jining, Shandong 272029, China
Zhang Jinguo
Department of Cardiology, the Affiliated Hospital of Jining Medical University, Shandong Provincial Key Laboratory for the Diagnosis and Treatment of Cardiac Diseases, Jining, Shandong 272029, China
Shen Caiyun
Department of Cardiology, the Affiliated Hospital of Jining Medical University, Shandong Provincial Key Laboratory for the Diagnosis and Treatment of Cardiac Diseases, Jining, Shandong 272029, China
Zhu Wenya
Clinical College of Jining Medical University, Jining, Shandong 272067, China
Du Chunlei
Department of Cardiology, the Affiliated Hospital of Jining Medical University, Shandong Provincial Key Laboratory for the Diagnosis and Treatment of Cardiac Diseases, Jining, Shandong 272029, China
