Cost 
$1,545.00
TAT 
4-6 weeks
CPT Code 
81405
Test Code 
2168
Test Methods 
Deletion/Duplication analysis
Specimen Types Accepted 
Blood
Saliva
Cultured Cells
Extracted DNA
Disorders 
Genes 
Notes 
If sending saliva, 2 kits are required.

Wolfram syndrome [OMIM#222300 and 604928] is a rare neurodegenerative disorder characterized by diabetes insipidus, diabetes mellitus, optic atrophy, and deafness. It is also known by the acronym of the key features of the disorder: DIDMOAD. Wolfram syndrome has been associated with mutations in both the WFS1 and CISD2 genes. Additional clinical findings may include renal abnormalities, ataxia, dementia, mental retardation and psychiatric illness. The minimal criteria for diagnosing Wolfram syndrome are juvenile onset diabetes mellitus and optic atrophy. Affected individuals described to date with CISD2 mutations do not have diabetes insipidus. Upper gastrointestinal ulceration and bleeding may occur in CISD2-related Wolfram syndrome. Some heterozygous mutations in WFS1 can be associated with phenotypic outcomes, including low-frequency non-syndromic deafness, or a Wolfram syndrome-like phenotype, with hearing impairment with diabetes mellitus and/or optic atrophy.

WFS1 encodes a glycoprotein called wolframin, which predominantly localizes to the endoplasmic reticulum. Mutations associated with Wolfram syndrome typically lead to a loss of protein function, whereas non-activating mutations have been identified in heterozygous carriers with autosomal dominant low frequency sensorineural hearing loss. CISD2 encodes an intermembrane protein in the endoplasmic reticulum. Although the CISD2 protein does not appear to directly interact with wolframin, they both appear to be involved in calcium homeostasis.