Molecular and genetic characterization of a large Brazilian cohort presenting hearing loss

Autor(es):Mostrar menos -

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]}

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: Human Genetics; OCT 2021.
• Citações Web of Science: 1

Resumo

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)

• Processo FAPESP: 14/13071-6 - Identificação de novos genes e estudos funcionais na surdez não-sindrômica
• Beneficiário: Karina Lezirovitz Mandelbaum
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/03433-9 - Utilização de células IPS e modelos animais para elucidação da fisiopatologia de perda auditiva sensorioneural pós-lingual de etiologia genética
• Beneficiário: Karina Lezirovitz Mandelbaum
• Modalidade de apoio: Auxílio à Pesquisa - Regular