OTOF
The Clinical Diagnostics Service of the Molecular Otolaryngology Research Laboratory is a Joint Commission-approved CLIA-accredited diagnostic laboratory that offers mutation screening of several genes.

DFNB9 (OMIM# 601071)
The gene OTOF causes autosomal recessive nonsyndromic hearing loss at the DFNB9 locus, which maps to chromosome 2p23-p22.

OTOF (OMIM# *603681)
OTOF is a gene of 48 exons that encodes a transmembrane protein of 1230 amino acids called otoferlin.  Otoferlin is expressed in multiple cell types within the cochlea.  More than 24 mutations in OTOF have been reported and are associated with autosomal recessive nonsyndromic sensorineural hearing loss.  Often, otoacoustic emissions (OAEs) are present while pure tone audiometry or auditory brain stem responses (ABRs) are grossly abnormal, features characteristic of auditory neuropathy.

MORL screening methodology
Screening for OTOF is performed by DHPLC and sequencing.  Oligonucleotide primers have been designed to amplify each exon.  Amplified samples are run on the DHPLC; abnormal elution profiles are sequenced to determine the specific mutation.  Exons carrying known SNPs are directly sequenced.

Sensitivity
Sensitivity is greater than 98%.

Turn-around time
Turn around time is approximately 3 months.

Cost: $1300

Indications for screening
This test is appropriate for any person with congenital hearing impairment and the diagnosis of auditory neuropathy, if the family history is consistent with autosomal recessive inheritance.  It is also appropriate for persons with congenital hearing impairment and a family history consistent with autosomal recessive inheritance if GJB2 mutation screening is negative.

GeneTests  GeneReviews – DFNB9 - Nonsyndromic Hearing Loss and Deafness

GeneTests  GeneReviews – DFNB1 - Nonsyndromic Hearing Loss and Deafness

References
Chaib, H et al.:  A gene responsible for a sensorineural nonsyndromic recessive deafness maps to chromosome 2p22-23. Hum. Molec. Genet. 5: 155-158, 1996.
PubMed ID:  8789454 
PubMed Search

Varga, R.;et al.:  Non-syndromic recessive auditory neuropathy is the result of mutations in the otoferlin (OTOF) gene. (Letter) J. Med. Genet. 40: 45-50, 2003.
PubMed ID: 12525542
PubMed Search