title: Intrafamilial phenotypic variability in families with biallelic SLC26A4 mutations.
abstract: OBJECTIVE
  Enlarged vestibular aqueduct (EVA) and hearing loss are known to be caused by SLC26A4 mutations, but large phenotypic variability exists among patients with biallelic SLC26A4 mutations. Intrafamilial phenotypic variability was analyzed in multiplex EVA families carrying biallelic SLC26A4 mutations to identify the contribution of SLC26A4 mutations and other genetic or environmental factors influencing the clinical manifestations.
  
  
  METHODS
  Retrospective case series.
  
  
  METHODS
  Eleven multiplex Korean families with EVA and hearing loss that carry biallelic mutations of the SLC26A4 gene were included. Genetic analysis for SLC26A4 and other genes including FOXI1, FOXI1-DBD, and KCNJ10 was performed. The auditory and other phenotypes were compared among siblings with the same SLC26A4 mutations.
  
  
  RESULTS
  The difference in the auditory phenotypes was identified between siblings in approximately half of the EVA families. Families with SLC26A4 mutations other than H723R homozygous mutations demonstrated more phenotypic variability, especially in those carrying IVS7-2A>G splice site mutation. Cochlear malformation was a consistent finding among siblings with the same SLC26A4 mutations. No mutation was identified in the FOXI1, FOXI1-DBD, and KCNJ10 genes in the tested families.
  
  
  CONCLUSIONS
  The possibility of variability concerning auditory phenotype should be considered even within family members carrying the same SLC26A4 mutations when providing genetic counseling to multiplex EVA families. Mutations in the currently known genes associated with EVA other than SLC26A4 were not found to be responsible for the intrafamilial phenotypic variability. Modifier genes or environmental factors other than the currently known genes seem to play a role in the phenotypic expressions of EVA patients.
authors: Department of Otorhinolaryngology, Kwandong University College of Medicine, Myongji Hospital, Goyang, South Korea.
authors: Mee Hyun
authors: MH
authors: Song
authors: Joong-Wook
authors: JW
authors: Shin
authors: Hong-Joon
authors: HJ
authors: Park
authors: Kyung-A
authors: KA
authors: Lee
authors: Yoonjung
authors: Y
authors: Kim
authors: Un-Kyung
authors: UK
authors: Kim
authors: Ju Hyun
authors: JH
authors: Jeon
authors: Jae Young
authors: JY
authors: Choi
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics; D001301:Audiometry, Pure-Tone; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D034381:Hearing Loss / Q000235:genetics*; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D056910:Republic of Korea; D012189:Retrospective Studies; D000076988:Sulfate Transporters; D014723:Vestibular Aqueduct / Q000002:abnormalities*
chemical_list: D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters
keywords: SLC26A4; enlarged vestibular aqueduct; hearing loss; mutation; variability