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

J Med Genet. 2018 Aug;55(8):555-560. doi: 10.1136/jmedgenet-2018-105349. Epub 2018 Apr 27.


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.

Keywords: ceacam16; deafness; non-syndromic hearing loss; splice-site.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Alternative Splicing*
  • Cell Adhesion Molecules / genetics*
  • Computational Biology / methods
  • Consanguinity
  • Genetic Association Studies* / methods
  • Genetic Predisposition to Disease*
  • Genetic Variation*
  • Genotype
  • Hearing Loss / genetics*
  • Humans
  • Iran
  • Middle Aged
  • Mutation
  • Pedigree
  • Phenotype*


  • Cell Adhesion Molecules
  • ceacam16 protein, human