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

BMC Endocrine Disorders

Wei Ren¹  Yunting Wang¹  Jixiu Yi²  Xuan Wang³  Ziyu Ren³  Dongfang Liu³  Qicong Liu³  Min Zhong⁴ 

[1] Department of Endocrinology and Metabolism, The First Affiliated Hospital of Chongqing Medical University, No. 1, You-Yi Rd, Yu-zhong District, 400010, Chongqing, China;Department of Endocrinology and Metabolism, The Qianjiang Central Hospital, Chongqing, China;Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Chongqing Medical University, No. 74, Linjiang Road, Yuzhong District, 400010, Chongqing, China;Department of Neurological Disorders, Chongqing Medical University Affiliated Children’s Hospital, Chongqing, China;

关键词: Wolfram syndrome;    Diabetes mellitus;    WFS1;    Compound heterozygous mutation;   

DOI  :  10.1186/s12902-021-00823-5

来源: Springer

【 摘 要 】

BackgroundWolfram 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.MethodsIn 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.ResultsWhen 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.ConclusionsThis 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.

【 授权许可】

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