| Full text | |
| Author(s): Show less - |
Batissoco, Ana Carla
[1, 2]
;
Pedroso-Campos, Vinicius
[1]
;
Pardono, Eliete
[1, 3]
;
Sampaio-Silva, Juliana
[1]
;
Sonoda, Cindy Yukimi
[1]
;
Vieira-Silva, Gleiciele Alice
[1]
;
da Silva de Oliveira Longati, Estefany Uchoa
[1]
;
Mariano, Diego
[4]
;
Hoshino, Ana Cristina Hiromi
[2]
;
Tsuji, Robinson Koji
[2]
;
Jesus-Santos, Rafaela
[1]
;
Abath-Neto, Osorio
[5]
;
Bento, Ricardo Ferreira
[1, 2]
;
Oiticica, Jeanne
[1, 2]
;
Lezirovitz, Karina
[1, 2]
Total Authors: 15
|
| Affiliation: | [1] Univ Sao Paulo, Lab Otorrinolaringol LIM 32, Hosp Clin HCFMUSP, Fac Med, Sao Paulo, SP - Brazil
[2] Univ Sao Paulo, ENT Dept, Hosp Clin, Fac Med, Sao Paulo, SP - Brazil
[3] Univ Paulista, Inst Ciencias Saude, Sao Paulo, SP - Brazil
[4] Univ Fed Minas Gerais, Dept Comp Sci, Belo Horizonte, MG - Brazil
[5] Univ Sao Paulo, Dept Neurol, Fac Med, FMUSP, Sao Paulo, SP - Brazil
Total Affiliations: 5
|
| Document type: | Journal article |
| Source: | Human Genetics; OCT 2021. |
| Web of Science Citations: | 1 |
| 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. (AU) | |
| FAPESP's process: | 14/13071-6 - Identification of novel genes and functional studies in nonsyndromic deafness |
| Grantee: | Karina Lezirovitz Mandelbaum |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 18/03433-9 - 145/5000 Use of IPS cells and animal models to elucidate the pathophysiology of post-lingual sensorineural hearing loss of genetic etiology |
| Grantee: | Karina Lezirovitz Mandelbaum |
| Support Opportunities: | Regular Research Grants |