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BMC Endocrine Disorders

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Open Access 01-12-2021 | Diabetes | Research article

Unique three-site compound heterozygous mutation in the WFS1 gene in Wolfram syndrome

Authors: Ziyu Ren, Jixiu Yi, Min Zhong, Yunting Wang, Qicong Liu, Xuan Wang, Dongfang Liu, Wei Ren

Published in: BMC Endocrine Disorders | Issue 1/2021

Abstract

Background

Wolfram syndrome (WFS) is a rare autosomal recessive genetic disease whose main cause is mutations in the WFS1 and CISD2 genes. Its characteristic clinical manifestations are diabetes insipidus, diabetes mellitus, optic atrophy and deafness.

Methods

In this study, two patients from this particular family underwent complete routine biochemical and ophthalmic tests. Blood, urine, routine stool test, visual acuity (VA) examination, visual field assessment, funduscope, optical coherence tomography and periorbital magnetic resonance imaging (MRI) scans were performed for each patient to evaluate whether the nerve fiber layer around the optic nerve head was atrophied and next-generation sequencing of target genes was performed in two patients.

Results

When the patients were diagnosed with Wolfram syndrome, their genetic analyses suggested unique three-site compound heterozygous mutations (c.2314C > T + c.2194C > T + c.2171C > T) in exon 8 of both patients’ chromosome 4. One mutation (c.2314C > T) was a novel mutation in the known reports of Wolfram syndrome. As a degenerative genetic disease, the types of gene mutations in the Chinese population are generally homozygous mutations at the unit point or compound heterozygous mutations at two nucleotide change sites. However, the two patients reported in this study are the first known cases of compound heterozygous mutations with three mutation sites coexisting on the WFS1 gene in China or even globally.

Conclusions

This study expands the phenotypic spectrum of Wolfram syndrome and may reveal a novel mutation pattern of pathogenesis of Wolfram syndrome. The implications of this discovery are valuable in the clinical diagnosis, prognosis, and treatment of patients with WFS1.

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Title: Unique three-site compound heterozygous mutation in the WFS1 gene in Wolfram syndrome
Authors: Ziyu Ren
Jixiu Yi
Min Zhong
Yunting Wang
Qicong Liu
Xuan Wang
Dongfang Liu
Wei Ren
Publication date: 01-12-2021
Publisher: BioMed Central
Keyword: Diabetes
Published in: BMC Endocrine Disorders / Issue 1/2021
Electronic ISSN: 1472-6823
DOI: https://doi.org/10.1186/s12902-021-00823-5

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