Open Access<i>SLC26A4</i> Genotypes and Phenotypes Associated with Enlargement of the Vestibular Aqueduct
Author(s) -
Taku Ito,
Byung Yoon Choi,
Kelly King,
Christopher Zalewski,
Julie Muskett,
Parna Chattaraj,
Thomas H. Shawker,
James C. Reynolds,
John A. Butman,
Carmen C. Brewer,
Philine Wangemann,
Seth L. Alper,
Andrew J. Griffith
Publication year - 2011
Publication title -
cellular physiology and biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.486
H-Index - 87
eISSN - 1421-9778
pISSN - 1015-8987
DOI - 10.1159/000335119
Subject(s) - vestibular aqueduct , goiter , medicine , allele , sensorineural hearing loss , hearing loss , mutation , endocrinology , pathology , genetics , thyroid , audiology , biology , gene
Enlargement of the vestibular aqueduct (EVA) is the most common inner ear anomaly detected in ears of children with sensorineural hearing loss. Pendred syndrome (PS) is an autosomal recessive disorder characterized by bilateral sensorineural hearing loss with EVA and an iodine organification defect that can lead to thyroid goiter. Pendred syndrome is caused by mutations of the SLC26A4 gene. SLC26A4 mutations may also be identified in some patients with nonsyndromic EVA (NSEVA). The presence of two mutant alleles of SLC26A4 is correlated with bilateral EVA and Pendred syndrome, whereas unilateral EVA and NSEVA are correlated with one (M1) or zero (M0) mutant alleles of SLC26A4. Thyroid gland enlargement (goiter) appears to be primarily dependent on the presence of two mutant alleles of SLC26A4 in pediatric patients, but not in older patients. In M1 families, EVA may be associated with a second, undetected SLC26A4 mutation or epigenetic modifications. In M0 families, there is probably etiologic heterogeneity that includes causes other than, or in addition to, monogenic inheritance.