Homozygosity mapping and direct sequencing identify a novel pathogenic variant in the CISD2 gene in an Iranian Wolfram syndrome family

摘要: Wolfram syndrome (WS) is a rare recessive neurodegenerative disorder characterized by diabetes mellitus and optic atrophy. Mortality morbidity rate of the disease high in adulthood due to neurological respiratory defects. So far, two WS genes, WFS1 (more than 90% cases) CISD2, have been identified. In present study, we aimed determine role WFS2 group Iranian families. We recruited 27 families with clinical diagnosis WS. Homozygosity mapping was implemented using short tandem repeat polymorphic markers bi-directional sequencing CISD2 gene negative for mutations. The candidate variant checked among family members. silico analysis protein modeling were applied assess pathogenic effect variant. Tetra-primers ARMS PCR set up checking 50 ethnic-matched controls. One showed homozygosity descent at WFS2. A novel missense variant, c.310T > C (p.S104P), found exon 2 gene. Computational predictions revealed its on structure, function, stability. Parents his healthy brother heterozygous not observed control group. This first study that elucidates disease-causing Next-generation could unravel genes remained expand genetic heterogeneity