A p.Val412Serfs pathogenic variant associated with Wolfram-like syndrome and leukodystrophy

Abstract Background Wolfram syndrome is due to a mutation of the WFS1 gene that codes for the transmembrane protein wolframin. This protein is located in the endoplasmic reticulum and is expressed at higher concentrations in the beta cells of pancreatic islets and the brain. The term "Wolfram syndrome spectrum" is often used because of its genetic and clinical heterogeneity. Disorders associated with the WFS1 gene include Wolfram syndrome following an autosomal recessive inheritance pattern and Wolfram-like syndrome following an autosomal dominant inheritance pattern, and congenital cataract. Here, we report a case with Wolfram-like syndrome presented with bilateral congenital cataract, optic atrophy, nystagmus, ataxia, mild intellectual disability, epilepsy and leukodystrophy. Case report Magnetic resonance imaging (MRI) showed bilateral cerebral T2 and flair hyperintensities that causes diffusion restriction in some areas with hypoperfusion. Bilateral T2 cerebellar central white matter hyperintensities and atrophy of brain stem were revealed by the brain MRI. There was also found evidence of a proximal cervical cord lesion and syrinx cavity in the vertebral MRI. The heterozygous frame-shift (c.1230_1233delCTCT; p.Val412Serfs) mutation in the WFS1 gene. This heterozygous pathogenic variant in the WFS1 gene was identified in both the father and grandmother. Conclusions To our knowledge, this is a novel Wolfram-like syndrome-related phenotype. This case report broadens the currently known phenotypic presentations of Wolfram-like syndrome and suggests that the p.Val412Serfs variant in the WFS1 gene may be associated with syrinx cavity and leukodystrophy.