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Old gene, new phenotype: splice-altering variants in CEACAM16 cause recessive non-syndromic hearing impairment

Abstract

Background Hearing loss is a genetically and phenotypically heterogeneous disorder.

Objectives The purpose of this study was to determine the genetic cause underlying the postlingual progressive hearing loss in two Iranian families.

Methods We used OtoSCOPE, a next-generation sequencing platform targeting >150 genes causally linked to deafness, to screen two deaf probands. Data analysis was completed using a custom bioinformatics pipeline, and variants were functionally assessed using minigene splicing assays.

Results We identified two homozygous splice-altering variants (c.37G>T and c.662–1G>C) in the CEACAM16 gene, segregating with the deafness in each family. The minigene splicing results revealed the c.37G>T results in complete skipping of exon 2 and loss of the AUG start site. The c.662–1G>C activates a cryptic splice site inside exon 5 resulting in a shift in the mRNA reading frame.

Conclusions These results suggest that loss-of-function mutations in CEACAM16 result in postlingual progressive hearing impairment and further support the role of CEACAM16 in auditory function.

  • deafness
  • ceacam16
  • non-syndromic hearing loss
  • splice-site

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