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Diagnostic outcomes of exome sequencing in patients with syndromic or non-syndromic hearing loss
- Source :
- PLoS ONE, PLoS ONE, Vol 13, Iss 1, p e0188578 (2018)
- Publication Year :
- 2018
- Publisher :
- Public Library of Science, 2018.
-
Abstract
- Hereditary hearing loss (HL) is a common sensory disorder, with an incidence of 1–2 per 1000 newborns, and has a genetic etiology in over 50% of cases. It occurs either as part of a syndrome or in isolation and is genetically very heterogeneous which poses a challenge for clinical and molecular diagnosis. We used exome sequencing to seek a genetic cause in a group of 56 subjects (49 probands) with HL: 32 with non-syndromic non-GJB2 HL and 17 with syndromic HL. Following clinical examination and clinical exome sequencing, an etiological diagnosis was established in 15 probands (15/49; 30%); eight (8/17;47%) from the syndromic group and seven (7/32; 21%) from the non-syndromic non-GJB2 subgroup. Fourteen different (half of them novel) non-GJB2 variants causing HL were found in 10 genes (CHD7, HDAC8, MITF, NEFL, OTOF, SF3B4, SLC26A4, TECTA, TMPRSS3, USH2A) among 13 probands, confirming the genetic heterogeneity of hereditary HL. Different genetic causes for HL were found in a single family while three probands with apparent syndromic HL were found to have HL as a separate clinical feature, distinct from the complex phenotype. Clinical exome sequencing proved to be an effective tool used to comprehensively address the genetic heterogeneity of HL, to detect clinically unrecognized HL syndromes, and to decipher complex phenotypes in which HL is a separate feature and not part of a syndrome.
- Subjects :
- 0301 basic medicine
Proband
Male
Molecular biology
lcsh:Medicine
Gene Sequencing
Otology
Deafness
Pathology and Laboratory Medicine
Sequencing techniques
Genotype
OTOF
Medicine and Health Sciences
Medicine
DNA sequencing
TECTA
lcsh:Science
Child
Hearing Disorders
Exome sequencing
Genetics
Multidisciplinary
medicine.diagnostic_test
Genomics
Syndrome
Phenotypes
Phenotype
Child, Preschool
Medical genetics
Female
Pathogens
Research Article
Adult
medicine.medical_specialty
Adolescent
03 medical and health sciences
Young Adult
Genomic Medicine
Diagnostic Medicine
Exome Sequencing
Humans
Genetic Testing
Hearing Loss
Genetic testing
Clinical Genetics
business.industry
Genetic heterogeneity
lcsh:R
Biology and Life Sciences
Human Genetics
Research and analysis methods
030104 developmental biology
Molecular biology techniques
Otorhinolaryngology
lcsh:Q
business
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 13
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....4d28a3a17ee1c2aaef62bf465461e5dd