Clinical Diagnostics Service – Genetic Deafness

Molecular Otolaryngology Research Laboratories

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

EYA1 encodes the protein EYES-ABSENT 1. EYA1 missense or nonsense mutations are found in approximately 30% of patients with a Branchio-Oto-Renal (BOR) syndrome phenotype. Approximately 20% of persons with EYA1 mutations segregate large deletions, duplications or rearrangements that are not easily detectable. A common EYA1 mutation has not been reported. Absence of a mutation in EYA1 in a person with a BOR syndrome phenotype does not exclude the diagnosis of BOR syndrome.

GJB2 encodes the protein CONNEXIN 26. GJB2 mutation screening is appropriate in all persons with congenital hearing impairment and a negative family history. Two large deletions that include a portion of GJB6 are included in this screen. 

MTRNR1 encodes the mitochondrial 12S ribosomal RNA protein. Hearing loss as a result of aminoglycoside exposure (OMIM# 58000) has been reported to involve at least two mutations in this gene, C1494T and A1555G. Damage to the inner ear is caused by reactive oxygen species, which provide a common pathway not only for aminoglycoside toxicity, but also for cisplatin toxicity and noise-induced hearing loss. MORL offers screening for both of these mutations.

MTTL1 encodes the mitochondrial transfer RNA-Leucine protein. The A3243G mutation has been found in several families segregating maternally inherited diabetes mellitus and sensorineural hearing loss. The A3243G mutation also is found in MELAS. In population studies of diabetics, the A3243G mutation is found in a small percent of patients.  

MTTS1 encodes the mitochondrial transfer RNA-Serine protein. The A7445G mutation has been found in several families with maternally inherited, progressive, nonsyndromic sensorineural deafness.  

POU3F4 encodes a transcription factor with a 75 amino acid POU domain and a 63 amino acid homeobox domain. Mutations in this gene or in the upstream sequence cause deafness at the DFN3 locus can be conductive (due to impaired stapes mobility) and/or mixed with a superimposed, often progressive, sensorineural component.  

SLC26A4 encodes the protein PENDRIN. SLC26A4 mutation screening is appropriate in persons with either Mondini dysplasia or dilated vestibular aqueduct syndrome. 

TECTA encodes the protein Alpha Tectorin.  Alpha Tectorin is the major non-collagenous component of the tectorial membrane.  In humans, mutations in TECTA cause both autosomal dominant and autosomal recessive nonsyndromic hearing loss.

WFS1 encodes the protein WOLFRAMIN. Mutations in WFS1 cause deafness at the DFNA 6/14 locus. This type of deafness is characterized by an audioprofile that shows familial low-frequency hearing loss. 

Contacts: richard-smith@uiowa.edu, jodi-klein@uiowa.edu, carla-nishimura@uiowa.edu, jessica-sorensen@uiowa.edu