Identification of novel likely pathogenic variant in CDH23 causing non-syndromic hearing loss, and a novel variant in OTOGL in an extended Iranian family
Background Sensorineural hearing loss (SNHL) is a clinically and genetically heterogeneous group of disorders of the auditory system. SNHL can occur as a symptom in more than 400 syndromes, and mutations in more than 150 genes can lead to SNHL. Mutations in the GJB2 and GJB6 genes are among the most...
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Published in | Egyptian Journal of Medical Human Genetics Vol. 25; no. 1; pp. 102 - 8 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Berlin/Heidelberg
Springer Berlin Heidelberg
14.09.2024
Springer Springer Nature B.V SpringerOpen |
Subjects | |
Online Access | Get full text |
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Summary: | Background
Sensorineural hearing loss (SNHL) is a clinically and genetically heterogeneous group of disorders of the auditory system. SNHL can occur as a symptom in more than 400 syndromes, and mutations in more than 150 genes can lead to SNHL. Mutations in the
GJB2
and
GJB6
genes are among the most common causes of SNHL worldwide. Mutations in Cadherin 23 (
CDH23)
can cause Usher syndrome and/or non-syndromic hearing loss (NSHL).
Material and methods
In this study, the Whole Exome Sequencing (WES) was used to detect the cause of hearing loss in a large consanguineous Iranian family with two patients. All family members underwent a thorough Genotype–phenotype correlation assessment and co-segregation analysis to understand the inheritance pattern within the family. The candidate variants were further confirmed by Sanger sequencing. In addition, in silico analysis was performed to predict the functional impact of the variants; the interpretation of the variants was performed in accordance with the American College of Medical Genetics (ACMG) guidelines.
Results
WES results identified two novel variants, a homozygous missense variant in
CDH23
(c.2961T > G) and a heterozygous splice site variant in
OTOGL
that was compatible with the autosomal recessive pattern of inheritance. Bioinformatics studies confirmed the pathogenic effects of novel variants. The c.2961T > G variant was classified as likely pathogenic.
Conclusions
The novel identified variant in the
CDH23
was the cause of congenital profound progressive form of HL. Samples were not available from the second family to distinguish which variant is responsible for the molecular pathology of the disease. Further studies and functional examinations are suggested for investigating the role of
OTOGL
: c. 1863-1G > T in deafness. |
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ISSN: | 1110-8630 2090-2441 |
DOI: | 10.1186/s43042-024-00578-3 |