A Novel Mutation in SLC26A4 Causes Nonsyndromic Autosomal Recessive Hearing Impairment.

Abstract

BACKGROUND:

Heterozygous mutations in GJB2 (MIM: 121011) encoding the gap junction protein connexin 26 are overrepresented in patient groups suffering from nonsyndromic sensorineural hearing impairment (HI) implying the involvement of additional genetic factors. Mutations in SLC26A4 (MIM: 605646), encoding the protein pendrin can cause both Pendred syndrome and autosomal recessive, nonsyndromic HI locus 4 type sensorineural HI (MIM: 600791).

OBJECTIVES:

Aim of this study was to investigate the role of SLC26A4 coding mutations in a nonsyndromic hearing impairment (NSHI) patient group bearing heterozygous GJB2 35delG mutations.

DESIGN:

We analyzed the 20 coding exons of SLC26A4 in a group of patients (n = 15) bearing heterozygous 35delG mutations and exclusively suffering from congenital HI.

RESULTS:

In a case of bilateral congenital hearing loss we identified a rare, novel SLC26A4 exon 2 splice donor mutation (c.164+1delG) predicted to truncate pendrin in the first cytoplasmic domain, as a compound heterozygote with the pathogenic missense mutation c.1061T>C (p.354F>S; rs111033243).

CONCLUSIONS:

Screening for SLC26A4 mutations may identify the genetic causes of hearing loss in patients bearing heterozygous mutations in GJB2.

HYPOTHESIS:

SLC26A4 coding mutations are genetic causes for nonsyndromic HI in patients bearing heterozygous GJB2 35delG mutations.

• Authors: Axel Wolf, Alexandra Frohne, Matthew Allen, Thomas Parzefall, Martin Koenighofer, Markus M Schreiner, Christian Schoefer, Klemens Frei, Trevor Lucas
• Journal: Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology (Otol Neurotol) Vol. 38 Issue 2 Pg. 173-179 (02 2017) ISSN: 1537-4505 [Electronic] United States
• PMID: 27861301 (Publication Type: Journal Article)

Chemical References

• Connexins
• GJB2 protein, human
• Membrane Transport Proteins
• SLC26A4 protein, human
• Sulfate Transporters
• Connexin 26

Topics

• Adult
• Child
• Child, Preschool
• Connexin 26
• Connexins (genetics)
• Exons
• Female
• Hearing Loss, Bilateral (genetics)
• Hearing Loss, Sensorineural (genetics)
• Heterozygote
• Humans
• Infant
• Male
• Membrane Transport Proteins (genetics)
• Middle Aged
• Mutation
• Sulfate Transporters
• Young Adult