Abstract
BackgroundWolfram Syndrome (WFS) is a rare autosomal recessive neurodegenerative disease which has a wide spectrum of manifestations including diabetes insipidus, diabetes mellitus, optic atrophy and deafness. WFS1 and CISD2 are two main causing genes of WFS. The aim of this study was to illustrate the ophthalmologic manifestations and determine the genotype of Chinese WFS patients.ResultsCompleted ophthalmic examinations and family investigations were performed on 4 clinically diagnosed WFS patients from 4 unrelated families. Genetic testing was done by the next generation sequencing of candidate genes. One patient carried a homozygous mutation (c.272_273del) in CISD2, two patients carried compound heterozygous mutations (c.1618 T > G + c.2020G > A and c.1048 T > A + c.2020G > A) in WFS1, and one patient carried a heterozygous mutation (c.937C > T) in WFS1. Three of them were novel mutations.ConclusionsOur study indicated WFS in Chinese is a neurodegenerative disease with both wide spectrum of clinical features and genetic heterogeneity. We found three novel mutations in WFS patients, and to our best knowledge, this is the first report of Chinese WFS patient with mutation in CISD2.
Highlights
Wolfram Syndrome (WFS) is a rare autosomal recessive neurodegenerative disease which has a wide spectrum of manifestations including diabetes insipidus, diabetes mellitus, optic atrophy and deafness
General clinical manifestations Four Chinese WFS patients from 4 different families were enrolled in our study
Patient 1 came from consanguineous family and has an elder brother diagnosed of diabetes mellitus (DM) at age of 10 years and died from ketosis encephalopathy at age of 17 years
Summary
Wolfram Syndrome (WFS) is a rare autosomal recessive neurodegenerative disease which has a wide spectrum of manifestations including diabetes insipidus, diabetes mellitus, optic atrophy and deafness. The main phenotypes of WFS are diabetes insipidus (DI), diabetes mellitus (DM), optic atrophy (OA) and deafness (D) [1, 3]. Around 50% patients harbor all these manifestations, so WFS was referred to as the acronym DIDMOAD syndrome [1, 3, 4]. Wolframin is widely expressed in neurons, pancreas, heart, muscle, liver, spleen and kidney [11]. It has been detected in optic nerve glial cells and retinal ganglion cells [12, 13]. The main function of wolframin are reducing the ER stress, maintaining the Ca2+ homeostasis and regulating the biosynthesis and secretion of insulin [14,15,16]
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