CAIO ROBLEDO D'ANGIOLI COSTA QUAIO
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- Mucopolysaccharidosis Type IVA: Evidence of Primary and Secondary Central Nervous System Involvement(2014) BORLOT, Felippe; ARANTES, Paula Ricci; QUAIO, Caio Robledo; FRANCO, Jose Francisco da Silva; LOURENCO, Charles Marques; GOMY, Israel; BERTOLA, Debora Romeo; KIM, Chong AeMucopolysaccharidosis type IVA is a rare lysosomal storage disease caused by a deficiency of N-acetylgalactosamine 6-sulfatase. Studies usually focus on skeletal abnormalities and their consequences. This study explores the neurological manifestations in a cohort of mucopolysaccharidosis type IVA patients, with a detailed focus on brain and spinal magnetic resonance imaging (MRI) findings. We performed a cross-sectional study involving nine patients with a biochemical confirmation of mucopolysaccharidosis type IVA. The protocol consists of a comprehensive clinical examination and brain and spinal cord MRI analysis for all subjects. The mean age was 16.4 years (+/- 5.7) and the mean onset of symptoms was 11.5 months (+/- 6.3). Overall, cognition was spared in all but one patient and motor weakness was a constant finding in all patients. Deep sensation impairment was found in six patients. The brain MRIs showed non-specific white matter changes in two patients. Other abnormalities such as clival hypoplasia, basilar invagination, and arachnoid cists appeared in seven of the nine patients. Eight patients presented spinal cord compression, and in three of them, two spinal levels were compromised. Odontoid hypoplasia and degenerative features in the neuroaxis were present in all patients. Our experience with mucopolysaccharidosis type IVA patients supports the evidence of central nervous system involvement. We emphasize the importance of regular clinical assessments with complete MRI studies, as an attempt to detect the early signs of spinal cord compression. This evaluation may be especially important before surgical interventions, as occult lesions may become symptomatic and promote postoperative unfavorable outcomes. (c) 2014 Wiley Periodicals, Inc.
- Gene expression profile suggesting immunological dysregulation in two Brazilian Bloom's syndrome cases(2020) MONTENEGRO, Marilia M.; QUAIO, Caio R.; PALMEIRA, Patricia; GASPARINI, Yanca; RANGEL-SANTOS, Andreia; DAMASCENO, Julian; NOVAK, Estela M.; GIMENEZ, Thamires M.; YAMAMOTO, Guilherme L.; RONJO, Rachel S.; NOVO-FILHO, Gil M.; CHEHIMI, Samar N.; ZANARDO, Evelin A.; DIAS, Alexandre T.; NASCIMENTO, Amom M.; COSTA, Thais V. M. M.; DUARTE, Alberto J. da S.; COUTINHO, Luiz L.; KIM, Chong A.; KULIKOWSKI, Leslie D.Background Bloom syndrome (BS) is a rare autosomal recessive chromosome instability disorder. The main clinical manifestations are growth deficiency, telangiectasic facial erythema, immunodeficiency, and increased risk to develop neoplasias at early age. Cytogenetic test for sister chromatid exchanges (SCEs) is used as a diagnostic marker for BS. In addition, most patients also present mutations in the & x202f;BLM & x202f;gene, related to defects in the DNA repair mechanism. However, the molecular mechanism behind the pathogenicity of BS is & x202f;still & x202f;not completely understood. Methods We describe two patients confirmed with BS by SCE and molecular analysis. Also, we performed the gene expression profile by the RNA-seq methodology in mRNA transcripts for differential gene expression analysis using as a biological condition for comparison BS versus health controls. Results We detected 216 differentially expressed genes related to immunological pathways such as positive regulation and activation of B cells, immune effector process and absence of difference of DNA repair genes expression. In addition; we also observed differentially expressed genes associated with apoptosis control, such as BCL2L1, CASP7, CDKN1A, E2F2, ITPR, CD274, TNFAIP6, TNFRSF25, TNFRSF13C, and TNFRSF17. Conclusion Our results suggest that the combination of altered expression of genes involved in signaling pathways of immune response and apoptosis control may contribute directly to the main characteristics observed in BS, such as recurrent infections, growth failure, and high risk of cancer. Transcriptome studies of other instability syndromes could allow a more accurate analysis of the relevant gene interactions associated with the destabilization of the genome. This is a first description of the profile of differential gene expression related to immunological aspects detected in patients with BS by RNA-seq.
- Report of a Large Brazilian Family With a Very Attenuated Form of Hunter Syndrome (MPS II)(2012) QUAIO, C. R. D. C.; GRINBERG, H.; VIEIRA, M. L. C.; PAULA, A. C.; LEAL, G. N.; GOMY, I.; LEISTNER-SEGAL, S.; GIUGLIANI, R.; BERTOLA, D. R.; KIM, C. A.Hunter syndrome, or Mucopolysaccharidosis type II (MPS II), is a rare X-linked recessive disorder caused by a deficiency of the lysosomal enzyme iduronate-2-sulfatase (IDS). The phenotypic spectrum varies from severe to attenuated clinical forms. We report a large Brazilian family with 16 affected individuals exhibiting a very attenuated form of MPS II. Fourteen female carriers were also identified. Twelve affected male patients, whose ages ranged from 1 to 35 years, were examined. Molecular analysis showed a novel missense mutation (p.A77D) in the IDS gene, confirming the diagnosis. Nine of the family members presented some degree of heart damage, though only the proband became symptomatic and required heart transplantation. One 19-year-old adult and 1-year-old twin boys each had a normal echocardiogram. Short stature was found in two adults while macrocephaly was found in one; the remaining adults had anthropometric measures within normal range. All affected adults had normal cognitive development and were able to perform normal daily activities, except one who had mild learning disability. Two patients died due to natural causes beyond 70 years of age. The female carriers did not present any signs of disease. In this large family with a mild form of MPS II and variable degree of clinical manifestations, it is noteworthy that several affected individuals have remained asymptomatic even at advanced age and even without enzyme replacement therapy.
- Vertebral segmentation defects in a Brazilian cohort: Clinical and molecular analysis focused on spondylocostal dysostosis(2022) LINNENKAMP, Bianca; GIRARDI, Raissa; ROCHA, Leticia; YAMAMOTO, Guilherme; CERONI, Jose Ricardo; MENDES, Antonia Elisabeth Cristhina; HONJO, Rachel; OLIVEIRA, Luiz Antonio; AMEMIYA, Raphael Bruno; QUAIO, Caio; OLIVEIRA FILHO, Joao Bosco de; KIM, Chong Ae; BERTOLA, Debora
- Frequency of carriers for rare recessive Mendelian diseases in a Brazilian cohort of 320 patients(2021) QUAIO, Caio Robledo D'Angioli Costa; CHUNG, Christine Hsiaoyun; PERAZZIO, Sandro Felix; DUTRA, Aurelio Pimenta; MOREIRA, Caroline Monaco; NOVO FILHO, Gil Monteiro; SACRAMENTO-BOBOTIS, Patricia Rossi; PENNA, Michele Groenner; SOUZA, Rafaela Rogerio Floriano de; CINTRA, Vivian Pedigone; CARNAVALLI, Juliana Emilia Prior; SILVA, Rafael Alves da; PAIXAO, Daniele; BARATELA, Wagner Antonio da Rosa; OLIVATI, Caroline; SPOLADOR, Gustavo Marquezani; SANTOS, Monize Nakamoto Provisor; PINTAO, Maria Carolina; FORNARI, Alexandre Ricardo dos Santos; BURGER, Matheus; RAMALHO, Rodrigo Fernandes; PEREIRA, Otavio Jose Eulalio; FERREIRA, Elisa Napolitano; MITNE-NETO, Miguel; KIM, Chong AeSeveral Mendelian disorders follow an autosomal recessive inheritance pattern. Epidemiological information on many inherited disorders may be useful to guide health policies for rare diseases, but it is often inadequate, particularly in developing countries. We aimed to calculate the carrier frequencies of rare autosomal recessive Mendelian diseases in a cohort of Brazilian patients using whole exome sequencing (WES). We reviewed the molecular findings of WES from 320 symptomatic patients who had carrier status for recessive diseases. Using the Hardy-Weinberg equation, we estimated recessive disease frequencies (q(2)) considering the respective carrier frequencies (2pq) observed in our study. We calculated the sensitivity of carrier screening tests based on lists of genes from five different clinical laboratories that offer them in Brazil. A total of 425 occurrences of 351 rare variants were reported in 278 different genes from 230 patients (71.9%). Almost half (48.8%) were carriers of at least one heterozygous pathogenic/likely pathogenic variant for rare metabolic disorders, while 25.9% of epilepsy, 18.1% of intellectual disabilities, 15.6% of skeletal disorders, 10.9% immune disorders, and 9.1% of hearing loss. We estimated that an average of 67% of the variants would not have been detected by carrier screening panels. The combined frequencies of autosomal recessive diseases were estimated to be 26.39/10,000 (or similar to 0.26%). This study shows the potential research utility of WES to determine carrier status, which may be a possible strategy to evaluate the clinical and social burden of recessive diseases at the population level and guide the optimization of carrier screening panels.
- Expansion and mechanistic insights into de novo DEAF1 variants in DEAF1-associated neurodevelopmental disorders(2023) MCGEE, Stacey R.; RAJAMANICKAM, Shivakumar; ADHIKARI, Sandeep; FALAYI, Oluwatosin C.; WILSON, Theresa A.; SHAYOTA, Brian J.; COLEMAN, Jessica A. Cooley; SKINNER, Cindy; CAYLOR, Raymond C.; STEVENSON, Roger E.; QUAIO, Caio Robledo D' Angioli Costa; WILKE, Berenice Cunha; BAIN, Jennifer M.; ANYANE-YEBOA, Kwame; BROWN, Kaitlyn; GREALLY, John M.; BIJLSMA, Emilia K.; RUIVENKAMP, Claudia A. L.; POLITI, Keren; ARBOGAST, Lydia A.; COLLARD, Michael W.; I, Jodi Huggenvik; ELSEA, Sarah H.; JENSIK, Philip J.De novo deleterious and heritable biallelic mutations in the DNA binding domain (DBD) of the transcription factor deformed epidermal autoregulatory factor 1 (DEAF1) result in a phenotypic spectrum of disorders termed DEAF1-associated neurodevelopmental disorders (DAND). RNA-sequencing using hippocampal RNA from mice with conditional deletion of Deaf1 in the central nervous system indicate that loss of Deaf1 activity results in the altered expression of genes involved in neuronal function, dendritic spine maintenance, development, and activity, with reduced dendritic spines in hippocampal regions. Since DEAF1 is not a dosage-sensitive gene, we assessed the dominant negative activity of previously identified de novo variants and a heritable recessive DEAF1 variant on selected DEAF1-regulated genes in 2 different cell models. While no altered gene expression was observed in cells over-expressing the recessive heritable variant, the gene expression profiles of cells over-expressing de novo variants resulted in similar gene expression changes as observed in CRISPR-Cas9-mediated DEAF1-deleted cells. Altered expression of DEAF1-regulated genes was rescued by exogenous expression of WT-DEAF1 but not by de novo variants in cells lacking endogenous DEAF1. De novo heterozygous variants within the DBD of DEAF1 were identified in 10 individuals with a phenotypic spectrum including autism spectrum disorder, developmental delays, sleep disturbance, high pain tolerance, and mild dysmorphic features. Functional assays demonstrate these variants alter DEAF1 transcriptional activity. Taken together, this study expands the clinical phenotypic spectrum of individuals with DAND, furthers our understanding of potential roles of DEAF1 on neuronal function, and demonstrates dominant negative activity of identified de novo variants.
conferenceObject Genomic study of non-syndromic hearing loss in unaffected individuals: frequency of pathogenic and likely pathogenic variants in a Brazilian cohort of 2097 genomes(2023) QUAIO, Caio Robledo; COELHO, Antonio Victor Campos; MOURA, Livia Maria Silva; GUEDES, Rafael Lucas Muniz; CHEN, Kelin; CERONI, Jose Ricardo Magliocco; MINILLO, Renata Moldenhauer; CARACIOLO, Marcel Pinheiro; REIS, Rodrigo de Souza; CERVATO, Murilo; ALMEIDA, Tatiana Ferreira de; OLIVEIRA FILHO, Joao Bosco deconferenceObject Reports of incidental findings in a cohort of 500 exomes of Brazilian patients were common and show potential impact in life-expectancy(2020) QUAIO, C. R. D. C.; MOREIRA, C. M.; SACRAMENTO-BOBOTIS, P. R.; NOVO-FILHO, G. M.; PENNA, M. G.; SOUSA, R. R. F.; TRINDADE, A. C. G.; FURUZAWA, C. R.; PEREIRA, D. P.; OLIVATI, C.; SPOLADOR, G. M.; PEREIRA, V. C.; SILVA, R. A.; SANTOS, M. N. P.; BARATELA, W. A. R.- Exome sequencing and targeted gene panels: a simulated comparison of diagnostic yield using data from 158 patients with rare diseases(2021) QUAIO, Caio Robledo D'Angioli Costa; OBANDO, Maria Jose Rivadeneira; PERAZZIO, Sandro Felix; DUTRA, Aurelio Pimenta; CHUNG, Christine Hsiaoyun; MOREIRA, Caroline Monaco; NOVO FILHO, Gil Monteiro; SACRAMENTO-BOBOTIS, Patricia Rossi; PENNA, Michele Groenner; SOUZA, Rafaela Rogerio Floriano de; CINTRA, Vivian Pedigone; CARNAVALLI, Juliana Emilia Prior; SILVA, Rafael Alves da; SANTOS, Monize Nakamoto Provisor; PAIXAO, Daniele; BARATELA, Wagner Antonio da Rosa; OLIVATI, Caroline; SPOLADOR, Gustavo Marquezani; PINTAO, Maria Carolina; FORNARI, Alexandre Ricardo dos Santos; BURGER, Matheus; RAMALHO, Rodrigo Fernandes; PEREIRA, Otavio Jose Eulalio; FERREIRA, Elisa Napolitano E; MITNE-NETO, Miguel; KIM, Chong AeNext-generation sequencing (NGS) has altered clinical genetic testing by widening the access to molecular diagnosis of genetically determined rare diseases. However, physicians may face difficulties selecting the best diagnostic approach. Our goal is to estimate the rate of possible molecular diagnoses missed by different targeted gene panels using data from a cohort of patients with rare genetic diseases diagnosed with exome sequencing (ES). For this purpose, we simulated a comparison between different targeted gene panels and ES: the list of genes harboring clinically relevant variants from 158 patients was used to estimate the theoretical rate of diagnoses missed by NGS panels from 53 different NGS panels from eight different laboratories. Panels presented a mean rate of missed diagnoses of 64% (range 14%-100%) compared to ES, representing an average predicted sensitivity of 36%. Metabolic abnormalities represented the group with highest mean of missed diagnoses (86%), while seizure represented the group with lowest mean (46%). Focused gene panels are restricted in covering select sets of genes implicated in specific diseases and they may miss molecular diagnoses of rare diseases compared to ES. However, their role in genetic diagnosis remains important especially for well-known genetic diseases with established genetic locus heterogeneity.
- Genomic study of nonsyndromic hearing loss in unaffected individuals: Frequency of pathogenic and likely pathogenic variants in a Brazilian cohort of 2,097 genomes(2022) QUAIO, Caio Robledo D' Angioli Costa; COELHO, Antonio Victor Campos; MOURA, Livia Maria Silva; GUEDES, Rafael Lucas Muniz; CHEN, Kelin; CERONI, Jose Ricardo Magliocco; MINILLO, Renata Moldenhauer; CARACIOLO, Marcel Pinheiro; REIS, Rodrigo de Souza; AZEVEDO, Bruna Mascaro Cordeiro de; NOBREGA, Maria Soares; TEIXEIRA, Anne Caroline Barbosa; LIMA, Matheus Martinelli; MOTA, Thamara Rayssa da; MATTA, Marina Cadena da; COLICHIO, Gabriela Borges Cherulli; RONCALHO, Aline Lulho; FERREIRA, Ana Flavia Martinho; CAMPILONGO, Gabriela Pereira; PERRONE, Eduardo; VIRMOND, Luiza do Amaral; MORENO, Carolina Araujo; PROTA, Joana Rosa Marques; FRANCA, Marina de; CERVATO, Murilo Castro; ALMEIDA, Tatiana Ferreira de; OLIVEIRA FILHO, Joao Bosco deHearing loss (HL) is a common sensory deficit in humans and represents an important clinical and social burden. We studied whole-genome sequencing data of a cohort of 2,097 individuals from the Brazilian Rare Genomes Project who were unaffected by hearing loss to investigate pathogenic and likely pathogenic variants associated with nonsyndromic hearing loss (NSHL). We found relevant frequencies of individuals harboring these alterations: 222 heterozygotes (10.59%) for sequence variants, 54 heterozygotes (2.58%) for copy-number variants (CNV), and four homozygotes (0.19%) for sequence variants. The top five most frequent genes and their corresponding combined allelic frequencies (AF) were GJB2 (AF = 1.57%), STRC (AF = 1%), OTOA (AF = 0.69%), TMPRSS3 (AF = 0.41%), and OTOF (AF = 0.29%). The most frequent sequence variant was GJB2:c.35del (AF = 0.72%), followed by OTOA:p. (Glu787Ter) (AF = 0.61%), while the most recurrent CNV was a microdeletion of 57.9 kb involving the STRC gene (AF = 0.91%). An important fraction of these individuals (n = 104; 4.96%) presented variants associated with autosomal dominant forms of NSHL, which may imply the development of some hearing impairment in the future. Using data from the heterozygous individuals for recessive forms and the Hardy-Weinberg equation, we estimated the population frequency of affected individuals with autosomal recessive NSHL to be 1:2,222. Considering that the overall prevalence of HL in adults ranges from 4-15% worldwide, our data indicate that an important fraction of this condition may be associated with a monogenic origin and dominant inheritance.