Spectrum of genetic variants in moderate to severe sporadic hearing loss in Pakistan
| Autor: | Sadaf Naz, P. Dane Witmer, Midhat Salman, Memoona Ramzan, Ghulam Mujtaba, Nara Sobreira, Rasheeda Bashir |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Candidate gene Genetic testing lcsh:Medicine Deafness 030105 genetics & heredity Consanguinity Sequencing Missense mutation Pakistan DNA sequencing lcsh:Science Child Exome sequencing Genetics Multidisciplinary medicine.diagnostic_test Homozygote Penetrance Phenotype Child Preschool Auditory system Audiometry Pure-Tone medicine.symptom Heterozygote Adolescent MYO7A Hearing loss Mutation Missense Article Young Adult 03 medical and health sciences Exome Sequencing Genetic variation otorhinolaryngologic diseases medicine Humans Genetic Predisposition to Disease Amino Acid Sequence Hearing Loss Genetic Association Studies business.industry lcsh:R Genetic Variation 030104 developmental biology Next-generation sequencing lcsh:Q Audiometry business Neuroscience |
| Zdroj: | Scientific Reports Scientific Reports, Vol 10, Iss 1, Pp 1-7 (2020) |
| ISSN: | 2045-2322 |
| Popis: | Hearing loss affects 380 million people worldwide due to environmental or genetic causes. Determining the cause of deafness in individuals without previous family history of hearing loss is challenging and has been relatively unexplored in Pakistan. We investigated the spectrum of genetic variants in hearing loss in a cohort of singleton affected individuals born to consanguineous parents. Twenty-one individuals with moderate to severe hearing loss were recruited. We performed whole-exome sequencing on DNA samples from the participants, which identified seventeen variants in ten known deafness genes and one novel candidate gene. All identified variants were homozygous except for two. Eleven of the variants were novel, including one multi-exonic homozygous deletion in OTOA. A missense variant in ESRRB was implicated for recessively inherited moderate to severe hearing loss. Two individuals were heterozygous for variants in MYO7A and CHD7, respectively, consistent with de novo variants or dominant inheritance with incomplete penetrance as the reason for their hearing loss. Our results indicate that similar to familial cases of deafness, variants in a large number of genes are responsible for moderate to severe hearing loss in sporadic individuals born to consanguineous couples. |
| Databáze: | OpenAIRE |
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