Wolfram's syndrome

Wolfram's syndrome:

• this is a rare autosomal recessive condition that predisposes to the development of type 1 diabetes mellitus (DM) and optic atrophy (OA)
• other clinical features can include diabetes insipidus (DI) and deafness D) (when these are present the condition is often referred to as DIDMOAD)
• other possible conditions that may occur include renal tract abnormalities, psychiatric disorders, short stature and hypogonadism
  • renal abnormalities associted with Wolfram's syndrome include hydrouteronephrosis and bladder abnormalities
• Wolfram syndrome is caused by a mutation in the WFS1 gene
  • the gene has been mapped to chromosome 4p16.1
    • WFS1 is an 8 exon gene encoding for a 890 amino-acid protein called wolframin
      • the wolframin protein is believed to code for a novel endoplasmic reticulum calcium channel.
  • inheritance of Wolfram's syndrome of two mutant alleles (i.e. it is an autosomal recessive disorder)

Reference:

1. Strom TM et al.. Diabetes insipidus, diabetes mellitus, optic atrophy and deafness (DIDMOAD) caused by mutations in novel gene (wolframin) coding for a predicted transmembrane protein. Hum Mol Genet 1998;7:2021-8.