Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Apr;141(3-4):455-464.
doi: 10.1007/s00439-021-02311-1. Epub 2021 Aug 3.

Genetic architecture and phenotypic landscape of SLC26A4-related hearing loss

Keiji Honda  1 , Andrew J Griffith  2
Affiliations
Review

Genetic architecture and phenotypic landscape of SLC26A4-related hearing loss

Keiji Honda et al. Hum Genet. 2022 Apr.

Abstract

Mutations of coding regions and splice sites of SLC26A4 cause Pendred syndrome and nonsyndromic recessive hearing loss DFNB4. SLC26A4 encodes pendrin, a transmembrane exchanger of anions and bases. The mutant SLC26A4 phenotype is characterized by inner ear malformations, including an enlarged vestibular aqueduct (EVA), incomplete cochlear partition type II and modiolar hypoplasia, progressive and fluctuating hearing loss, and vestibular dysfunction. A thyroid iodine organification defect can lead to multinodular goiter and distinguishes Pendred syndrome from DFNB4. Pendred syndrome and DFNB4 are each inherited as an autosomal recessive trait caused by biallelic mutations of SLC26A4 (M2). However, there are some EVA patients with only one detectable mutant allele (M1) of SLC26A4. In most European-Caucasian M1 patients, there is a haplotype that consists of 12 variants upstream of SLC26A4, called CEVA (Caucasian EVA), which acts as a pathogenic recessive allele in trans to mutations affecting the coding regions or splice sites of SLC26A4. This combination of an M1 genotype with the CEVA haplotype is associated with a less severe phenotype than the M2 genotype. The phenotype in EVA patients with no mutant alleles of SLC26A4 (M0) has a very low recurrence probability and is likely to be caused by other factors.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Albert S, Blons H, Jonard L, Feldmann D, Chauvin P, Loundon N, Sergent-Allaoui A, Houang M, Joannard A, Schmerber S, Delobel B, Leman J, Journel H, Catros H, Dollfus H, Eliot MM, David A, Calais C, Drouin-Garraud V, Obstoy MF, Tran Ba Huy P, Lacombe D, Duriez F, Francannet C, Bitoun P, Petit C, Garabedian EN, Couderc R, Marlin S, Denoyelle F (2006) SLC26A4 gene is frequently involved in nonsyndromic hearing impairment with enlarged vestibular aqueduct in Caucasian populations. Eur J Hum Genet 14:773–779. https://doi.org/10.1038/sj.ejhg.5201611 - DOI - PubMed
    1. Antonelli PJ, Nall AV, Lemmerling MM, Mancuso AA, Kubilis PS (1998) Hearing loss with cochlear modiolar defects and large vestibular aqueducts. Am J Otol 19:306–312 - PubMed
    1. Azaiez H, Yang T, Prasad S, Sorensen JL, Nishimura CJ, Kimberling WJ, Smith RJ (2007) Genotype-phenotype correlations for SLC26A4-related deafness. Hum Genet 122:451–457. https://doi.org/10.1007/s00439-007-0415-2 - DOI - PubMed
    1. Baldwin CT, Weiss S, Farrer LA, De Stefano AL, Adair R, Franklyn B, Kidd KK, Korostishevsky M, Bonné-Tamir B (1995) Linkage of congenital, recessive deafness (DFNB4) to chromosome 7q31 and evidence for genetic heterogeneity in the Middle Eastern Druze population. Hum Mol Genet 4:1637–1642. https://doi.org/10.1093/hmg/4.9.1637 - DOI - PubMed
    1. Berrettini S, Forli F, Bogazzi F, Neri E, Salvatori L, Casani AP, Franceschini SS (2005) Large vestibular aqueduct syndrome: audiological, radiological, clinical, and genetic features. Am J Otolaryngol 26:363–371. https://doi.org/10.1016/j.amjoto.2005.02.013 - DOI - PubMed

Substances

Supplementary concepts

LinkOut - more resources