A novel WFS1 variant associated with severe diabetic retinopathy in Wolfram syndrome type 1

Wolfram syndrome type 1 is a rare neurodegenerative disorder including diabetes insipidus, diabetes mellitus, optic atrophy, and deafness, with variable additional findings. The phenotypic spectrum is very heterogeneous, with non-autoimmune juvenile-onset diabetes and optic atrophy as minimal criter...

Full description

Saved in:
Bibliographic Details
Published in:Ophthalmic genetics 2023-06, Vol.44 (3), p.304-312
Main Authors: Maamouri, Rym, Hizem, Syrine, Kammoun, Ines, Elaribi, Yasmina, Rejeb, Imen, Sebai, Molka, Jilani, Houweyda, Rouzier, Cécile, Cheour, Monia, Paquis-Flucklinger, Véronique, Ben Jemaa, Lamia
Format: Article
Language:English
Subjects:
Diabetic Retinopathy - diagnosis
Diabetic Retinopathy - genetics
Humans
Mutation
Mutation, Missense
Optic Atrophy - genetics
Wolfram Syndrome - diagnosis
Wolfram Syndrome - genetics
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Wolfram syndrome type 1 is a rare neurodegenerative disorder including diabetes insipidus, diabetes mellitus, optic atrophy, and deafness, with variable additional findings. The phenotypic spectrum is very heterogeneous, with non-autoimmune juvenile-onset diabetes and optic atrophy as minimal criteria for the diagnosis. Biallelic mutations in the gene are the causative genetic anomaly for the syndrome, with, however, no evident genotype-phenotype correlation. Among the clinical features of the disease, diabetic retinopathy depicts a rarely reported microvascular complication. In this report, we describe the clinical and genetic findings in a 26-year-old patient presenting with Wolfram syndrome and severe diabetic retinopathy. The mutation screening was performed by polymerase chain reaction followed by Sanger sequencing of the entire coding sequence of the gene. A novel homozygous missense variant c.1901A>T (p.Lys634Met) was found in the proband and classified as probably pathogenic according to the American College of Medical Genetics and Genomics. The molecular study of the gene is essential for the diagnostic confirmation, to provide appropriate genetic counseling and a mutational screening in the at-risk relatives. The c.1901A>T (p.Lys634 Met) is a novel variant that could be responsible for a severe form of Wolfram syndrome with early and proliferative diabetic retinopathy.
ISSN:1381-6810
1744-5094
DOI:10.1080/13816810.2022.2113546