TY - JOUR T1 - Old gene, new phenotype: splice-altering variants in <em>CEACAM16</em> cause recessive non-syndromic hearing impairment JF - Journal of Medical Genetics JO - J Med Genet DO - 10.1136/jmedgenet-2018-105349 SP - jmedgenet-2018-105349 AU - Kevin T Booth AU - Kimia Kahrizi AU - Hossein Najmabadi AU - Hela Azaiez AU - Richard JH Smith Y1 - 2018/04/26 UR - http://jmg.bmj.com/content/early/2018/04/26/jmedgenet-2018-105349.abstract N2 - 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 &gt;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&gt;T and c.662–1G&gt;C) in the CEACAM16 gene, segregating with the deafness in each family. The minigene splicing results revealed the c.37G&gt;T results in complete skipping of exon 2 and loss of the AUG start site. The c.662–1G&gt;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. ER -