A CLINICAL CASE REPORT: A NOVEL WFS1 VARIANT ASSOCIATED WITH EARLY-ONSET DIABETES IN TWO AFFECTED SIBLINGS
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Abstract
This case report describes a family with two children affected by early-onset diabetes mellitus (DM), who underwent clinical evaluation and molecular genetic analysis. The family has two children, a son born in 2003 and a daughter born in 2005, both diagnosed with early-onset DM and currently receiving insulin therapy. Genetic analysis revealed that both siblings carried the homozygous WFS1 variant c.1320_1323dup (p.Thr442ArgfsTer102), which results in a frameshift. This variant had not been reported in ClinVar at the time of analysis but was classified as pathogenic according to the 2015 ACMG/AMP guidelines. Both parents were heterozygous carriers of the variant and were clinically unaffected. We report a novel WFS1 variant associated with early-onset DM in a family with two affected siblings. These findings are important for establishing a definitive diagnosis, providing recurrence-risk counselling, and guiding reproductive planning, particularly for families considering in vitro fertilization (IVF) combined with preimplantation genetic testing for monogenic disorders (PGT-M).
Keywords
WFS1 gene, Monogenic diabetes, Wolfram syndrome, Novel variant, Frameshift, PGT-M
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References
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