title: SLC26A4mutation testing for hearing loss associated with enlargement of the vestibular aqueduct.
abstract: Pendred syndrome (PS) is characterized by autosomal recessive inheritance of goiter associated with a defect of iodide organification, hearing loss, enlargement of the vestibular aqueduct (EVA), and mutations of theSLC26A4gene. However, not all EVA patients have PS orSLC26A4mutations. Two mutant alleles ofSLC26A4are detected in ¼ of North American or European EVA populations, one mutant allele is detected in another ¼ of patient populations, and no mutations are detected in the other ½. The presence of two mutant alleles ofSLC26A4is associated with abnormal iodide organification, increased thyroid gland volume, increased severity of hearing loss, and bilateral EVA. The presence of a single mutant allele ofSLC26A4is associated with normal iodide organification, normal thyroid gland volume, less severe hearing loss and either bilateral or unilateral EVA. When other underlying correlations are accounted for, the presence of a cochlear malformation or the size of EVA does not have an effect on hearing thresholds. This is consistent with observations of anSlc26a4mutant mouse model of EVA in which hearing loss is independent of endolymphatic hydrops or inner ear malformations. Segregation analyses of EVA in families suggest that the patients carrying one mutant allele ofSLC26A4have a second, undetected mutant allele ofSLC26A4, and the probability of a sibling having EVA is consistent with its segregation as an autosomal recessive trait. Patients without any mutations are an etiologically heterogeneous group in which siblings have a lower probability of having EVA.SLC26A4mutation testing can provide prognostic information to guide clinical surveillance and management, as well as the probability of EVA affecting a sibling.
authors.affiliation: Otolaryngology Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850, United States.
authors.forename: Taku
authors.initials: T
authors.lastname: Ito
authors.affiliation: Otolaryngology Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850, United States.
authors.forename: Julie
authors.initials: J
authors.lastname: Muskett
authors.affiliation: Otolaryngology Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850, United States.
authors.forename: Parna
authors.initials: P
authors.lastname: Chattaraj
authors.affiliation: Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850, United States.
authors.forename: Byung Yoon
authors.initials: BY
authors.lastname: Choi
authors.affiliation: Otolaryngology Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850, United States.
authors.forename: Kyu Yup
authors.initials: KY
authors.lastname: Lee
authors.affiliation: Otolaryngology Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850, United States.
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Zalewski
authors.affiliation: Otolaryngology Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850, United States.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: King
authors.affiliation: Anatomy and Physiology Department, Kansas State University, Manhattan, KS 66506, United States.
authors.forename: Xiangming
authors.initials: X
authors.lastname: Li
authors.affiliation: Anatomy and Physiology Department, Kansas State University, Manhattan, KS 66506, United States.
authors.forename: Philine
authors.initials: P
authors.lastname: Wangemann
authors.affiliation: Diagnostic Radiology Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892, United States.
authors.forename: Thomas
authors.initials: T
authors.lastname: Shawker
authors.affiliation: Otolaryngology Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850, United States.
authors.forename: Carmen C
authors.initials: CC
authors.lastname: Brewer
authors.affiliation: Renal Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States.
authors.forename: Seth L
authors.initials: SL
authors.lastname: Alper
authors.affiliation: Otolaryngology Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850, United States.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Griffith
keywords: Genetic testing; Genotype-phenotype correlation; Goiter; Hearing loss; Pendred syndrome; SLC26A4; Vestibular aqueduct