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
3 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.
- A rare genomic duplication in 2p14 underlies autosomal dominant hearing loss DFNA58(2020) LEZIROVITZ, Karina; VIEIRA-SILVA, Gleiciele A.; BATISSOCO, Ana C.; LEVY, Debora; KITAJIMA, Joao P.; TROUILLET, Alix; OUYANG, Ellen; ZEBARJADI, Navid; SAMPAIO-SILVA, Juliana; PEDROSO-CAMPOS, Vinicius; NASCIMENTO, Larissa R.; SONODA, Cindy Y.; BORGES, Vinicius M.; VASCONCELOS, Laura G.; BECK, Roberto M. O.; GRASEL, Signe S.; JAGGER, Daniel J.; GRILLET, Nicolas; BENTO, Ricardo F.; MINGRONI-NETTO, Regina C.; OITICICA, JeanneHere we define a similar to 200 Kb genomic duplication in 2p14 as the genetic signature that segregates with postlingual progressive sensorineural autosomal dominant hearing loss (HL) in 20 affected individuals from the DFNA58 family, first reported in 2009. The duplication includes two entire genes, PLEK and CNRIP1, and the first exon of PPP3R1 (protein coding), in addition to four uncharacterized long non-coding (lnc) RNA genes and part of a novel protein-coding gene. Quantitative analysis of mRNA expression in blood samples revealed selective overexpression of CNRIP1 and of two lncRNA genes (LOC107985892 and LOC102724389) in all affected members tested, but not in unaffected ones. Qualitative analysis of mRNA expression identified also fusion transcripts involving parts of PPP3R1, CNRIP1 and an intergenic region between PLEK and CNRIP1, in the blood of all carriers of the duplication, but were heterogeneous in nature. By in situ hybridization and immunofluorescence, we showed that Cnrip1, Plek and Ppp3r1 genes are all expressed in the adult mouse cochlea including the spiral ganglion neurons, suggesting changes in expression levels of these genes in the hearing organ could underlie the DFNA58 form of deafness. Our study highlights the value of studying rare genomic events leading to HL, such as copy number variations. Further studies will be required to determine which of these genes, either coding proteins or non-coding RNAs, is or are responsible for DFNA58 HL.
- 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.