Complete Paternal Uniparental Isodisomy of Chromosome 4 in a Patient with Isolated Optic Neuropathy

Wolfram syndrome (WS) is a rare progressive neurodegenerative disease with optic atrophy being one of the defining clinical features. This syndrome is also known by its historical acronym of DIDMOAD (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and Deafness). The majority of cases are due to biallelic variants in WFS1 (4p16.3), encoding an endoplasmic reticulum membrane protein. Complete uniparental isodisomy (iUPD) is a rare genetic phenomenon resulting in two identical chromosomes originating from a single parental allele. If the latter carries a pathogenic variant in a recessive gene, it can lead to a recessive disorder manifesting itself as a non-Mendelian trait. Here, we report a case of paternal iUPD of chromosome 4 resulting in WS.