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

ABSTRACT

Background

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.

Methods

The mutation screening was performed by polymerase chain reaction followed by Sanger sequencing of the entire coding sequence of the WFS1 gene.

Results

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.

Conclusions

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.

KEYWORDS:

• Wolfram syndrome
• diabetes mellitus
• diabetic retinopathy
• WFS1 gene
• genetic variation

Acknowledgments

The authors would like to acknowledge the patient and his family for their cooperation and their consent to publication.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Consent for publication

The patient signed informed consent regarding publishing his data and photographs.

Ethics approval

This study was approved by the Ethical Committee of Mongi Slim Hospital under the ID 06/2022.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/13816810.2022.2113546.

Additional information

Funding

The author(s) reported that there is no funding associated with the work featured in this article.