Identification of pathogenic mutations for a Wolfram syndrome pedigree by whole exome sequencing and analysis of its clinical characteristics

Objective·To identify the causative gene and mutations and describe the clinical traits in a Chinese diabetes pedigree suspected of Wolfram syndrome.Methods·A total of 12 subjects from one family were included. The proband was admitted to the Department of Endocrinology, The First Affiliated Hospital of Xinxiang Medical University, for the first time in May 2013. Then he visited the hospital for follow-up in July 2022 and in April 2023, respectively. The other members of this family included the proband′s sister, father, mother, paternal grandfather, paternal grandmother, uncle, aunt, as well as maternal grandfather, maternal grandmother, and two brothers of the proband′s mother. Clinical data of all subjects were collected. The whole exome sequencing was used to screen the pathogenic genes and mutation sites of six members of the family, and Sanger sequencing was used to verify the above results. Effects of the mutation of the pathogenic gene WFS1 in Wolfram syndrome on the function of the wolframin protein