{Reference Type}: Case Reports
{Title}: A novel WFS1 variant associated with severe diabetic retinopathy in Wolfram syndrome type 1.
{Author}: Maamouri R;Hizem S;Kammoun I;Elaribi Y;Rejeb I;Sebai M;Jilani H;Rouzier C;Cheour M;Paquis-Flucklinger V;Ben Jemaa L;
{Journal}: Ophthalmic Genet
{Volume}: 44
{Issue}: 3
{Year}: 06 2023 12
{Factor}: 1.274
{DOI}: 10.1080/13816810.2022.2113546
{Abstract}: 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 WFS1 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.<BR>The mutation screening was performed by polymerase chain reaction followed by Sanger sequencing of the entire coding sequence of the WFS1 gene.<BR>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.<BR>The molecular study of the WFS1 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.