JEANNE DA ROSA OITICICA RAMALHO
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/32 - Laboratório de Otorrinolaringologia, Hospital das Clínicas, Faculdade de Medicina
LIM/32 - Laboratório de Otorrinolaringologia, Hospital das Clínicas, Faculdade de Medicina
7 resultados
Resultados de Busca
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- NCOA3 identified as a new candidate to explain autosomal dominant progressive hearing loss (vol 29, pg 3691, 2020)(2022) SALAZAR-SILVA, R.; DANTAS, Vitor Lima Goes; ALVES, Leandro Ucela; BATISSOCO, Ana Carla; OITICICA, Jeanne; LAWRENCE, Elizabeth A.; KAWAFI, Abdelwahab; YANG, Yushi; NICASTRO, Fernanda Stavale; NOVAES, Beatriz Caiuby; HAMMOND, Chrissy; KAGUE, Erika; MINGRONI-NETTO, R. C.
- Molecular and genetic characterization of a large Brazilian cohort presenting hearing loss(2022) BATISSOCO, Ana Carla; PEDROSO-CAMPOS, Vinicius; PARDONO, Eliete; SAMPAIO-SILVA, Juliana; SONODA, Cindy Yukimi; VIEIRA-SILVA, Gleiciele Alice; LONGATI, Estefany Uchoa da Silva de Oliveira; MARIANO, Diego; HOSHINO, Ana Cristina Hiromi; TSUJI, Robinson Koji; JESUS-SANTOS, Rafaela; ABATH-NETO, Osorio; BENTO, Ricardo Ferreira; OITICICA, Jeanne; LEZIROVITZ, KarinaHearing 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.
bookPart Etiologia da Deficiência Auditiva(2014) OITICICA, Jeanne; LEZIROVITZ, Karina; BATISSOCO, Ana CarlabookPart Surdez Neonatal de Origem Genética(2014) OITICICA, Jeanne; LEZIROVITZ, Karina; BATISSOCO, Ana Carla- Stem-cell therapy for hearing loss: are we there yet?(2019) DUFNER-ALMEIDA, Luiz Gustavo; CRUZ, Dayane Bernardino da; MINGRONI NETTO, Regina Celia; BATISSOCO, Ana Carla; OITICICA, Jeanne; SALAZAR-SILVA, RodrigoIntroduction: Mammalian hair cells and auditory neurons do not show regenerative capacity. Hence, damage to these cell types is permanent and leads to hearing loss. However, there is no treatment that re-establishes auditory function. Regenerative therapies using stem cells represent a promising alternative. Objective: This article aims to review the current literature about the main types of stem cells with potential for application in cell therapy for sensorineural hearing loss, the most relevant experiments already performed in animals, as well as the advances that have been recently made in the field. Methods: Research included the databases PubMed/MEDLINE, Web of Science, Science Direct and SciELO, as well as gray literature. Search strategy included the following main terms: ""stem cells'', ""hair cells'' and ""auditory neurons''. Additionally, the main terms were combined with the following secondary terms: ""mesenchymal'', ""iPS'', ""inner ear'', ""auditory''. The research was conducted independently by three researchers. Results: Differentiation of stem cells into hair cells and auditory neurons has a high success rate, reaching up to 82% for the first and 100% for the latter. Remarkably, these differentiated cells are able to interact with hair cells and auditory neurons of cochlear explants through formation of new synapses. When transplanted into the cochlea of animals with hearing loss, auditory restoration has been documented to date only in deafferented animals. Conclusion: Advances have been more prominent in cases of auditory neuropathy, since partial improvement of auditory nerve conditions through cell-based therapy may increase the number of patients who can successfully receive cochlear implants. (C) 2019 Associacao Brasileira de Otorrinolaringologia e Cirurgia Cervico-Facial.
- Exome Sequencing Identifies a Novel Nonsense Mutation of MYO6 as the Cause of Deafness in a Brazilian Family(2018) SAMPAIO-SILVA, Juliana; BATISSOCO, Ana Carla; JESUS-SANTOS, Rafaela; ABATH-NETO, Osorio; SCARPELLI, Luciano Cesar; NISHIMURA, Patricia Yoshie; GALINDO, Layla Testa; BENTO, Ricardo Ferreira; OITICICA, Jeanne; LEZIROVITZ, KarinaWe investigated 313 unrelated subjects who presented with hearing loss to identify the novel genetic causes of this condition in Brazil. Causative GJB2/GJB6 mutations were found in 12.7% of the patients. Among the familial cases (100/313), four were selected for exome sequencing. In one case, two novel heterozygous variants were found and were predicted to be pathogenic based on bioinformatics tools, that is, p.Ser906* (MYO6) and p.Arg42Cys (GJB3). We confirmed that this nonsense MYO6 mutation segregated with deafness in this family. Only the proband and her unaffected mother exhibited the GJB3 mutation, which is in the same amino acid of a known Erythrokeratodermia variabilis mutation. None of the patients exhibited this skin disease, but the proband exhibited a more severe hearing loss. Hence, the GJB3 mutation was considered to be a variant of uncertain significance. In conclusion, we described a novel nonsense MYO6 mutation that was responsible for the hearing loss in a Brazilian family. This mutation resides in the neck domain of myosin-VI after the motor domain. Thus, our data give further support for genotype-phenotype correlations, which state that when the motor domain of the protein is functioning, the hearing loss is milder and has a later onset. The three remaining families without mutations in the known genes suggest that there are still deafness genes to be revealed.
- NCOA3 identified as a new candidate to explain autosomal dominant progressive hearing loss(2020) SILVA, Rodrigo Salazar da; DANTAS, Vitor Lima Goes; ALVES, Leandro Ucela; BATISSOCO, Ana Carla; OITICICA, Jeanne; LAWRENCE, Elizabeth A.; KAWAFI, Abdelwahab; YANG, Yushi; NICASTRO, Fernanda Stavale; NOVAES, Beatriz Caiuby; HAMMOND, Chrissy; KAGUE, Erika; MINGRONI NETTO, Regina CeliaHearing loss is a frequent sensory impairment in humans and genetic factors account for an elevated fraction of the cases. We have investigated a large family of five generations, with 15 reported individuals presenting non-syndromic, sensorineural, bilateral and progressive hearing loss, segregating as an autosomal dominant condition. Linkage analysis, using SNP-array and selected microsatellites, identified a region of near 13 cM in chromosome 20 as the best candidate to harbour the causative mutation. After exome sequencing and filtering of variants, only one predicted deleterious variant in the NCOA3 gene (NM_181659, c.2810C> G; p.Ser937Cys) fit in with our linkage data. RT-PCR, immunostaining and in situ hybridization showed expression of ncoa3 in the inner ear of mice and zebrafish. We generated a stable homozygous zebrafish mutant line using the CRISPR/Cas9 system. ncoa3-/- did not display any major morphological abnormalities in the ear, however, anterior macular hair cells showed altered orientation. Surprisingly, chondrocytes forming the ear cartilage showed abnormal behaviour in ncoa3-/-, detaching from their location, invading the ear canal and blocking the cristae. Adult mutants displayed accumulation of denser material wrapping the otoliths of ncoa3-/- and increased bone mineral density. Altered zebrafish swimming behaviour corroborates a potential role of ncoa3 in hearing loss. In conclusion, we identified a potential candidate gene to explain hereditary hearing loss, and our functional analyses suggest subtle and abnormal skeletal behaviour as mechanisms involved in the pathogenesis of progressive sensory function impairment.