Journal article
Molecular and genetic characterization of a large Brazilian cohort presenting hearing loss
Human genetics, Vol.141(3-4), pp.519-538
04/01/2022
DOI: 10.1007/s00439-021-02372-2
PMID: 34599368
Abstract
Hearing loss is one of the most common sensory defects, affecting 5.5% of the worldwide population and significantly impacting health and social life. It is mainly attributed to genetic causes, but their relative contribution reflects the geographical region's socio-economic development. Extreme genetic heterogeneity with hundreds of deafness genes involved poses challenges for molecular diagnosis. Here we report the investigation of 542 hearing-impaired subjects from all Brazilian regions to search for genetic causes. Biallelic GJB2/GJB6 causative variants were identified in 12.9% (the lowest frequency was found in the Northern region, 7.7%), 0.4% carried GJB2 dominant variants, and 0.6% had the m.1555A > G variant (one aminoglycoside-related). In addition, other genetic screenings, employed in selected probands according to clinical presentation and presumptive inheritance patterns, identified causative variants in 2.4%. Ear malformations and auditory neuropathy were diagnosed in 10.8% and 3.5% of probands, respectively. In 3.8% of prelingual/perilingual cases, Waardenburg syndrome was clinically diagnosed, and in 71.4%, these diagnoses were confirmed with pathogenic variants revealed; seven out of them were novel, including one CNV. All these genetic screening strategies revealed causative variants in 16.2% of the cases. Based on causative variants in the molecular diagnosis and genealogy analyses, a probable genetic etiology was found in similar to 50% of the cases. The present study highlights the relevance of GJB2/GJB6 as a cause of hearing loss in all Brazilian regions and the importance of screening unselected samples for estimating frequencies. Moreover, when a comprehensive screening is not available, molecular diagnosis can be enhanced by selecting probands for specific screenings.
Details
- Title: Subtitle
- Molecular and genetic characterization of a large Brazilian cohort presenting hearing loss
- Creators
- Ana Carla Batissoco - Hospital das Clínicas da Faculdade de Medicina da Universidade de São PauloVinicius Pedroso-Campos - Hospital das Clínicas da Faculdade de Medicina da Universidade de São PauloEliete Pardono - Hospital das Clínicas da Faculdade de Medicina da Universidade de São PauloJuliana Sampaio-Silva - Hospital das Clínicas da Faculdade de Medicina da Universidade de São PauloCindy Yukimi Sonoda - Hospital das Clínicas da Faculdade de Medicina da Universidade de São PauloGleiciele Alice Vieira-Silva - Hospital das Clínicas da Faculdade de Medicina da Universidade de São PauloEstefany Uchoa da Silva de Oliveira Longati - Hospital das Clínicas da Faculdade de Medicina da Universidade de São PauloDiego Mariano - Universidade Federal de Minas GeraisAna Cristina Hiromi Hoshino - Hospital das Clínicas da Faculdade de Medicina da Universidade de São PauloRobinson Koji Tsuji - Hospital das Clínicas da Faculdade de Medicina da Universidade de São PauloRafaela Jesus-Santos - Hospital das Clínicas da Faculdade de Medicina da Universidade de São PauloOsorio Abath-Neto - Universidade de São PauloRicardo Ferreira Bento - Hospital das Clínicas da Faculdade de Medicina da Universidade de São PauloJeanne Oiticica - Hospital das Clínicas da Faculdade de Medicina da Universidade de São PauloKarina Lezirovitz - Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
- Resource Type
- Journal article
- Publication Details
- Human genetics, Vol.141(3-4), pp.519-538
- Publisher
- Springer Nature
- DOI
- 10.1007/s00439-021-02372-2
- PMID
- 34599368
- ISSN
- 0340-6717
- eISSN
- 1432-1203
- Number of pages
- 20
- Grant note
- 573920/2008-7 / Brazilian National Council for Scientific and Technological Development (CNPq, Brasilia, Brazil); Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ) 2014/13071-6; 2018/03433-9 / Sao Paulo Research Foundation (FAPESP, Sao Paulo, Brazil); Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
- Language
- English
- Date published
- 04/01/2022
- Academic Unit
- Pathology
- Record Identifier
- 9984276456002771
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