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

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

Author information

1
Molecular Otolaryngology Renal Research Laboratories, Department of Otolaryngology, University of Iowa, Iowa City, Iowa, USA.
2
The Interdisciplinary Graduate Program in Molecular Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
3
Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Islamic Republic of Iran.
#
Contributed equally

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.

KEYWORDS:

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

PMID:
29703829
PMCID:
PMC6060001
[Available on 2019-08-01]
DOI:
10.1136/jmedgenet-2018-105349

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