SLC26A4
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.

DFNB4 (OMIM#: 600791) and Pendred syndrome (OMIM#: 274600)
DFNB4
Baldwin and colleagues reported linkage of a family with recessive, nonsyndromic deafness to chromosome 7q31 in 1995 and designated this locus as DFNB4. Mutations in SLC26A4 are causally related to deafness at this locus. Inner ear computed tomography has shown that DFNB4 includes dilation of the endolymphatic duct (DVA, also called enlarged vestibular aqueduct syndrome, EVA [OMIM# 600791]).

Pendred Syndrome 
Pendred syndrome (OMIM#: 274600) is a common syndromic form of hearing loss (Fraser 1965). Clinical features include inner ear abnormalities, sensorineural hearing loss and diffuse thyroid enlargement or goiter. Inner ear computed tomography has shown that the Pendred Syndrome phenotype includes dilation of the endolymphatic duct and sac, enlargement of the vestibular aqueduct and cochlear dysplasia. This constellation of anomalies is known as Mondini malformation or Mondini dysplasia.

SLC26A4 (encoding Pendrin) 
Mutations in SLC26A4 (OMIM#: 605646) cause Pendred Syndrome. Over 150 mutations have been described (http://www.healthcare.uiowa.edu/labs/pendredandbor/). The gene is a member of the solute carrier gene family and functions as an anion carrier. It has 21 exons and the encoded protein, called Pendrin, has 780 amino acids.

MORL screening methodology
Screening for SLC26A4 is performed by DHPLC and sequencing. Oligonucleotide primers have been designed to amplify each exon. Abnormal elution profiles are sequenced to determine the specific mutation.

DHPLC profile of SLC26A4, Exon 14

Legend: Profiles in brown, green and light green contain mutations; profile in black is wild type.

Sensitivity
Sensitivity is greater than 99%.

Turn-around time
Turn around time is approximately 8 weeks.

Cost: $500

Indications for screening
This test is appropriate for any person with congenital sensorineural hearing loss and an inner ear abnormality by computed tomography (DVA, EVA, Mondini dysplasia).

GeneTests  GeneReviews – Branchiootorenal Syndrome

References
Pendred, V.: Deaf mutism and goitre.Lancet. 1896;ii:532.

 

Fraser, G. R. : Association of congenital deafness with goiter (Pendred's syndrome): a study of 207 families. Ann. Hum. Genet. 28: 201-249, 1965.
PubMed ID: 14304636
PubMed Search

Campbell, C. et al.: Pendred syndrome, DFNB4, and PDS/SLC26A4 identification of eight novel mutations and possible genotype-phenotype correlations. Hum. Mutat. 17: 403-411, 2001.
PubMed ID: 11317356
PubMed Search

Prasad, S. et al.: Pendred syndrome and DFNB4-mutation screening of SLC26A4 by denaturing high-performance liquid chromatography and the identification of eleven novel mutations. Am. J. Hum. Genet. 2004 Jan 1;124(1):1-9.
PubMed ID: 14679580
PubMed Search

Pendred and BOR Homepage: http://www.medicine.uiowa.edu/pendredandbor/