TY - JOUR

T1 - Association of SLC26A4 mutations, morphology, and hearing in pendred syndrome and NSEVA

AU - Mey, Kristianna

AU - Muhamad, Ali A

AU - Tranebjaerg, Lisbeth

AU - Rendtorff, Nanna D

AU - Rasmussen, Stig H

AU - Bille, Michael

AU - Cayé-Thomasen, Per

N1 - © 2018 The American Laryngological, Rhinological and Otological Society, Inc.

PY - 2019/11

Y1 - 2019/11

N2 - OBJECTIVE: To investigate the relations of monoallelic (M1), biallelic (M2), or the absence of mutations (M0) in SLC26A4 to inner ear morphology and hearing levels in individuals with Pendred syndrome (PS) or nonsyndromic enlarged vestibular aqueduct (NSEVA) associated with hearing loss.METHODS: In a cohort of 139 PS/NSEVA individuals, 115 persons from 95 unrelated families had full genetic sequencing of SLC26A4, and 113 had retrievable images for re-assessment of inner ear morphology. The association between the number of mutant alleles in SLC26A4, inner ear morphology (including endolymphatic sac size and protein content on magnetic resonance imaging), and hearing level (pure tone average) was explored.RESULTS: Biallelic SLC26A4 mutations (M2) occurred in three-quarters of the cohort and was invariably associated with poor hearing; in 87%, it was associated with incomplete partition type II of the cochlea as well as enlarged endolymphatic sac and vestibular aqueduct. M1 or M0 individuals exhibited a greater variability in inner ear morphology. Endolymphatic sac size and presence of "high-protein" sac contents were significantly higher in M2 individuals compared to M1 and M0 individuals.CONCLUSION: The number of SLC26A4 mutations is associated with severity and variability of inner ear morphology and hearing level in individuals with PS or NSEVA. M2 individuals have poorer hearing and present largely incomplete partition type II of the cochleas with enlarged endolymphatic sacs, whereas individuals with M1 and no detectable SLC26A4 mutations have less severe hearing loss and more diverse inner ear morphology.LEVEL OF EVIDENCE: 4. Laryngoscope, 129:2574-2579, 2019.

AB - OBJECTIVE: To investigate the relations of monoallelic (M1), biallelic (M2), or the absence of mutations (M0) in SLC26A4 to inner ear morphology and hearing levels in individuals with Pendred syndrome (PS) or nonsyndromic enlarged vestibular aqueduct (NSEVA) associated with hearing loss.METHODS: In a cohort of 139 PS/NSEVA individuals, 115 persons from 95 unrelated families had full genetic sequencing of SLC26A4, and 113 had retrievable images for re-assessment of inner ear morphology. The association between the number of mutant alleles in SLC26A4, inner ear morphology (including endolymphatic sac size and protein content on magnetic resonance imaging), and hearing level (pure tone average) was explored.RESULTS: Biallelic SLC26A4 mutations (M2) occurred in three-quarters of the cohort and was invariably associated with poor hearing; in 87%, it was associated with incomplete partition type II of the cochlea as well as enlarged endolymphatic sac and vestibular aqueduct. M1 or M0 individuals exhibited a greater variability in inner ear morphology. Endolymphatic sac size and presence of "high-protein" sac contents were significantly higher in M2 individuals compared to M1 and M0 individuals.CONCLUSION: The number of SLC26A4 mutations is associated with severity and variability of inner ear morphology and hearing level in individuals with PS or NSEVA. M2 individuals have poorer hearing and present largely incomplete partition type II of the cochleas with enlarged endolymphatic sacs, whereas individuals with M1 and no detectable SLC26A4 mutations have less severe hearing loss and more diverse inner ear morphology.LEVEL OF EVIDENCE: 4. Laryngoscope, 129:2574-2579, 2019.

KW - Adolescent

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Alleles

KW - Child

KW - Cochlea/pathology

KW - Ear, Inner/pathology

KW - Endolymphatic Sac/pathology

KW - Female

KW - Goiter, Nodular/genetics

KW - Hearing/genetics

KW - Hearing Loss, Sensorineural/genetics

KW - Hearing Tests

KW - Humans

KW - Male

KW - Middle Aged

KW - Mutation

KW - Retrospective Studies

KW - Sulfate Transporters/genetics

KW - Vestibular Aqueduct/abnormalities

KW - Young Adult

KW - genotype vs. phenotype

KW - inner ear morphology

KW - nonsyndromic enlarged vestibular aqueduct

KW - DFNB4

KW - EVA

KW - Pendred syndrome

KW - SLC26A4

UR - http://www.scopus.com/inward/record.url?scp=85071634517&partnerID=8YFLogxK

U2 - 10.1002/lary.27319

DO - 10.1002/lary.27319

M3 - Journal article

VL - 129

SP - 2574

EP - 2579

JO - The Laryngoscope

JF - The Laryngoscope

SN - 0023-852X

IS - 11

ER -