Preferred Minimum: 8 mL whole blood Absolute Minimum: 4 mL whole blood

DFNA6/14/38 and Wolfram Syndrome DFNA6/14/38 Three overlapping DFNA loci have been mapped to 4p16 - DFNA6, DFNA14 and DFNA38 (Lesperance 1995, Van Camp 1999, Young 2001). All are associated with mutations in WFS1. Now referred to as the DFNA6/14/38 locus, the phenotype is very distinctive and is characterized by low frequency hearing loss that rises to normal in the high frequencies. Some persons report tinnitus, but not vertigo. Wolfram Syndrome Mutations in WFS1 also cause Wolfram Syndrome, a recessively inherited disorder with a phenotype that includes diabetes insipidus, diabetes mellitus, optic atrophy and deafness (also known as DIDMOAD syndrome). Studies have shown an association betweenWFS1 mutations and diabetes mellitus and psychiatric illness. WFS1 The gene, WFS1, contains 8 exons; exons 2 -7 encode the 890 amino acid protein Wolframin. The majority of mutations causing low frequency hearing loss are in the C-terminal portion of the protein; mutations causing Wolfram Syndrome are spread throughout the gene (Cryns et al., 2003). Sensitivity is greater than 98%.