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Metabolic Brain Disease

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04-04-2023 | Original Article

Mucopolysaccharidosis type IIIC in chinese mainland: clinical and molecular characteristics of ten patients and report of six novel variants in the HGSNAT gene

Authors: Yingjun Liang, Xiaolan Gao, Deyun Lu, Huiwen Zhang, Zhang

Published in: Metabolic Brain Disease | Issue 6/2023

Abstract

Background

Mucopolysaccharidosis type IIIC (MPS IIIC; Sanfilippo syndrome C) is a rare lysosomal storage disease caused by mutations in the heparan-α-glucosaminide N-acetyltransferase (HGSNAT) gene, resulting in the accumulation of heparan sulfate. MPS IIIC is characterized by severe neuropsychiatric symptoms and mild somatic symptoms.

Methods

Our study analyzed the clinical presentation and biochemical characteristics of ten Chinese MPS IIIC patients from eight families. Whole exome sequencing was applied to identify the variants in HGSNAT gene. In one patient with only one mutant allele identified firstly, whole genome sequencing was applied. The pathogenic effect of novel variants was evaluated in silico.

Results

The mean age at the onset of clinical symptoms was 4.2 ± 2.5 years old, and the mean age of diagnosis was 7.6 ± 4.5 years old, indicating a delay of diagnosis. The most common onset symptoms were speech deterioration, and the most frequent presenting symptoms are speech deterioration, mental deterioration, hyperactivity and hepatomegaly, sequentially. All mutant alleles of 10 patients have been identified. There were eleven different HGSNAT variants, and the most common one was a previously reported variant c.493 + 1G > A. There were six novel variants, p.R124T, p.G290A, p.G426E, c.743 + 101_743 + 102delTT, c.851 + 171T > A and p.V582Yfs*18 in our cohort. Extraordinarily, two deep intron variants were identified in our cohort, with the variant c.851 + 171T > A identified by whole genome sequencing.

Conclusion

This study analyzed the clinical, biochemical, and genetic characteristics of ten Chinese MPS IIIC patients, which would assist in the early diagnosis and genetic counselling of MPS IIIC.

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Title: Mucopolysaccharidosis type IIIC in chinese mainland: clinical and molecular characteristics of ten patients and report of six novel variants in the HGSNAT gene
Authors: Yingjun Liang
Xiaolan Gao
Deyun Lu
Huiwen Zhang
Zhang
Publication date: 04-04-2023
Publisher: Springer US
Published in: Metabolic Brain Disease / Issue 6/2023
Print ISSN: 0885-7490
Electronic ISSN: 1573-7365
DOI: https://doi.org/10.1007/s11011-023-01204-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Mucopolysaccharidosis type IIIC in chinese mainland: clinical and molecular characteristics of ten patients and report of six novel variants in the HGSNAT gene

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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