Specimen:

Whole Blood

Collection Medium:

Minimum:

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

Analytic Time:

3 months

Reference Range:

None detected

Interpretive Data:

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%.

Comments:

Please print, complete and submit the Deafness Testing Requisition 
from the Molecular Otolaryngology & Renal Research Laboratory, to 
Specimen Control/Mailouts with the specimen and the Epic Requisition.

Methodology:

Screening for WFS1 is performed by DHPLC and sequencing. 
Oligonucleotide primers have been designed to amplify each coding exon 
(2-8). Amplified samples are resolved by DHPLC; abnormal elution 
profiles are sequenced to identify the specific mutation. Because exon 
8 of WFS1 (aa 289-891) contains many non-disease causing polymorphisms, 
it is sequenced directly using overlapping primer sets.

CPT Code:

83891, 83894, 83898 (x8), 83903 (x6), 83904 (x8), 83912