RT Journal Article SR Electronic T1 Old gene, new phenotype: splice-altering variants in CEACAM16 cause recessive non-syndromic hearing impairment JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP jmedgenet-2018-105349 DO 10.1136/jmedgenet-2018-105349 A1 Kevin T Booth A1 Kimia Kahrizi A1 Hossein Najmabadi A1 Hela Azaiez A1 Richard JH Smith YR 2018 UL http://jmg.bmj.com/content/early/2018/04/26/jmedgenet-2018-105349.abstract AB 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.