m.h.s. and j.-w.s. contributed equally to this work.
Intrafamilial phenotypic variability in families with biallelic SLC26A4 mutations
Version of Record online: 13 DEC 2013
© 2013 The American Laryngological, Rhinological and Otological Society, Inc.
Volume 124, Issue 5, pages E194–E202, May 2014
How to Cite
Song, M. H., Shin, J.-W., Park, H.-J., Lee, K.-A., Kim, Y., Kim, U.-K., Jeon, J. H. and Choi, J. Y. (2014), Intrafamilial phenotypic variability in families with biallelic SLC26A4 mutations. The Laryngoscope, 124: E194–E202. doi: 10.1002/lary.24504
This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology (MEST; 2012R1A1A1015761) and by an NRF grant funded by the Korean government (MEST; 2011-0028066).
The authors have no other funding, financial relationships, or conflicts of interest to disclose.
- Issue online: 18 APR 2014
- Version of Record online: 13 DEC 2013
- Accepted manuscript online: 7 NOV 2013 02:25AM EST
- Manuscript Accepted: 30 OCT 2013
- Manuscript Revised: 26 SEP 2013
- Manuscript Received: 2 MAY 2013
- enlarged vestibular aqueduct;
- hearing loss;
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.
Retrospective case series.
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.
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.
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.
Level of Evidence
NA Laryngoscope, 124:E194–E202, 2014