MATHEUS AUGUSTO ARAUJO CASTRO
Índice h a partir de 2011
4
Projetos de Pesquisa
Unidades Organizacionais
Instituto da Criança, Hospital das Clínicas, Faculdade de Medicina - Médico
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
12 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 12
- Sanfilippo syndrome type B: Analysis of patients diagnosed by the MPS Brazil Network(2022) MONTENEGRO, Yorran Hardman Araujo; SOUZA, Carolina Fischinger Moura de; KUBASKI, Francyne; TRAPP, Franciele Barbosa; BURIN, Maira Graeff; MICHELIN-TIRELLI, Kristiane; LEISTNER-SEGAL, Sandra; FACCHIN, Ana Carolina Brusius; MEDEIROS, Fernanda S.; GIUGLIANI, Luciana; RIBEIRO, Erlane Marques; LOURENCO, Charles Marques; CARDOSO-DOS-SANTOS, Augusto Cesar; RIBEIRO, Marcia Goncalves; KIM, Chong Ae; CASTRO, Matheus Augusto Araujo; EMBIRUCU, Emilia Katiane; STEINER, Carlos Eduardo; MOREIRA, Maria Lucia Castro; MONTANO, Hector Quintero; BALDO, Guilherme; GIUGLIANI, RobertoMucopolysaccharidosis type IIIB is a rare autosomal recessive disorder characterized by deficiency of the enzyme N-acetyl-alpha-d-glucosaminidase (NAGLU), caused by biallelic pathogenic variants in the NAGLU gene, which leads to storage of heparan sulfate and a series of clinical consequences which hallmark is neurodegeneration. In this study clinical, epidemiological, and biochemical data were obtained from MPS IIIB patients diagnosed from 2004-2019 by the MPS Brazil Network (""Rede MPS Brasil""), which was created with the goal to provide an easily accessible and comprehensive investigation of all MPS types. One hundred and ten MPS IIIB patients were diagnosed during this period. Mean age at diagnosis was 10.9 years. Patients were from all over Brazil, with a few from abroad, with a possible cluster of MPS IIIB identified in Ecuador. All patients had increased urinary levels of glycosaminoglycans and low NAGLU activity in blood. Main clinical symptoms reported at diagnosis were coarse facies and neurocognitive regression. The most common variant was p.Leu496Pro (30% of alleles). MPS IIIB seems to be relatively frequent in Brazil, but patients are diagnosed later than in other countries, and reasons for that probably include the limited awareness about the disease by health professionals and the difficulties to access diagnostic tests, factors that the MPS Brazil Network is trying to mitigate.
- Phenotypic, molecular, and functional characterization of COQ7-related primary CoQ10 deficiency: Hypomorphic variants and two distinct disease entities(2023) WONGKITTICHOTE, Parith; LASIO, Maria Laura Duque; MAGISTRATI, Martina; PATHAK, Sheel; SAMPLE, Brooke; CARVALHO, Daniel Rocha; ORTEGA, Adriana Banzzatto; CASTRO, Matheus Augusto Araujo; GUSMAO, Claudio M. de; TOLER, Tomi L.; BELLACCHIO, Emanuele; DALLABONA, Cristina; SHINAWI, MarwanPrimary coenzyme Q10 (CoQ10) deficiency is a group of inborn errors of metabolism caused by defects in CoQ10 biosynthesis. Biallelic pathogenic variants in COQ7, encoding mitochondrial 5-demethoxyubiquinone hydroxy-lase, have been reported in nine patients from seven families. We identified five new patients with COQ7- related primary CoQ10 deficiency, performed clinical assessment of the patients, and studied the functional effects of current and previously reported COQ7 variants and potential treatment options. The main clinical features included a neonatal-onset presentation with severe neuromuscular, cardiorespiratory and renal involve-ment and a late-onset disease presenting with progressive neuropathy, lower extremity weakness, abnormal gait, and variable developmental delay. Baker's yeast orthologue of COQ7, CAT5, is required for growth on oxida-tive carbon sources and cat5 & UDelta; strain demonstrates oxidative growth defect. Expression of wild-type CAT5 could completely rescue the defect; however, yeast CAT5 harboring equivalent human pathogenic variants could not. Interestingly, cat5 & UDelta; yeast harboring p.Arg57Gln (equivalent to human p.Arg54Gln), p.Arg112Trp (equivalent to p.Arg107Trp), p.Ile69Asn (equivalent to p.Ile66Asn) and combination of p.Lys108Met and p.Leu116Pro (equiva-lent to the complex allele p.[Thr103Met;Leu111Pro]) partially rescued the growth defects, indicating these var-iants are hypomorphic alleles. Supplementation with 2,4 dihydroxybenzoic acid (2,4-diHB) rescued the growth defect of both the leaky and severe mutants. Overexpression of COQ8 and 2,4-diHB supplementation synergisti-cally restored oxidative growth and respiratory defect. Overall, we define two distinct disease presentations of COQ7-related disorder with emerging genotype-phenotype correlation and validate the use of the yeast model for functional studies of COQ7 variants. & COPY; 2023 Published by Elsevier Inc.
- Stroke in vascular Ehlers-Danlos syndrome(2023) MARTINS, Rebecca Ranzani; PAIVA, Mauricio Leonardo da Silva; TEIXEIRA, Weverton Carlos da Silva; KAWAHIRA, Rachel Sayuri Honjo; FREUA, Fernando; CASTRO, Matheus Augusto Araujo; KIM, Chong Ae; KOK, Fernando
- Mystery solved after 23 years: M syndrome is PIGT-associated multiple congenital anomalies-hypotonia-seizures syndrome 3(2022) NOBREGA, Paulo Ribeiro; CASTRO, Matheus Augusto Araujo; PAIVA, Anderson Rodrigues Brandao de; KOK, Fernando
- De novo pathogenic DHX30 variants in two cases(2021) MIYAKE, Noriko; KIM, Chong Ae; HAGINOYA, Kazuhiro; CASTRO, Matheus Augusto Araujo; HONJO, Rachel Sayruri; MATSUMOTO, Naomichi
- Novel CLTC variants cause new brain and kidney phenotypes(2022) ITAI, Toshiyuki; MIYATAKE, Satoko; TSUCHIDA, Naomi; SAIDA, Ken; NARAHARA, Sho; TSUYUSAKI, Yu; CASTRO, Matheus Augusto Araujo; KIM, Chong Ae; OKAMOTO, Nobuhiko; UCHIYAMA, Yuri; KOSHIMIZU, Eriko; HAMANAKA, Kohei; FUJITA, Atsushi; MIZUGUCHI, Takeshi; MATSUMOTO, NaomichiHeterozygous variants in CLTC, which encode the clathrin heavy chain protein, cause neurodevelopmental delay of varying severity, and often accompanied by dysmorphic features, seizures, hypotonia, and ataxia. To date, 28 affected individuals with CLTC variants have been reported, although their phenotypes have not been fully elucidated. Here, we report three novel de novo CLTC (NM_001288653.1) variants in three individuals with previously unreported clinical symptoms: c.3662_3664del:p.(Leu1221del) in individual 1, c.2878T>C:p.(Trp960Arg) in individual 2, and c.2430+1G>T:p.(Glu769_Lys810del) in individual 3. Consistent with previous reports, individuals with missense or small in-frame variants were more severely affected. Unreported symptoms included a brain defect (cystic lesions along the lateral ventricles of the brain in individuals 1 and 3), kidney findings (high-echogenic kidneys in individual 1 and agenesis of the left kidney and right vesicoureteral reflux in individual 3), respiratory abnormality (recurrent pneumonia in individual 1), and abnormal hematological findings (anemia in individual 1 and pancytopenia in individual 3). Of note, individual 1 even exhibited prenatal abnormality (fetal growth restriction, cystic brain lesions, high-echogenic kidneys, and a heart defect), suggesting that CLTC variants should be considered when abnormal prenatal findings in multiple organs are detected.
- Phenotype-genotype analysis of 242 individuals with RASopathies: 18-year experience of a tertiary center in Brazil(2020) BERTOLA, Debora R.; CASTRO, Matheus A. A.; YAMAMOTO, Guilherme L.; HONJO, Rachel S.; CERONI, Jose Ricardo; BUSCARILLI, Michele M.; FREITAS, Amanda B.; MALAQUIAS, Alexsandra C.; PEREIRA, Alexandre C.; JORGE, Alexander A. L.; PASSOS-BUENO, Maria Rita; KIM, Chong A.We report the clinical and molecular data of a large cohort comprising 242 individuals with RASopathies, from a single Tertiary Center in Brazil, the largest study from Latin America. Noonan syndrome represented 76% of the subjects, with heterozygous variants in nine different genes, mainly PTPN11, SOS1, RAF1, LZTR1, and RIT1, detected by Sanger and next-generation sequencing. The latter was applied to 126 individuals, with a positive yield of 63% in genes of the RAS/MAPK cascade. We present evidence that there are some allelic differences in PTPN11 across distinct populations. We highlight the clinical aspects that pose more medical concerns, such as the cardiac anomalies, bleeding diathesis and proliferative lesions. The genotype-phenotype analysis between the RASopathies showed statistically significant differences in some cardinal features, such as craniofacial and cardiac anomalies, the latter also statistically significant for different genes in Noonan syndrome. We present two individuals with a Noonan syndrome phenotype, one with an atypical, structural cardiac defect, harboring variants in genes mainly associated with isolated hypertrophic cardiomyopathy and discuss the role of these variants in their phenotype.
- Disease progression in Sanfilippo type B: Case series of Brazilian patients(2024) MONTENEGRO, Yorran Hardman Araujo; KUBASKI, Francyne; TRAPP, Franciele Barbosa; RIEGEL-GIUGLIANI, Mariluce; SOUZA, Carolina Fischinger Moura de; RIBEIRO, Erlane Marques; LOURENCO, Charles Marques; CARDOSO-DOS-SANTOS, Augusto Cesar; RIBEIRO, Marcia Goncalves; KIM, Chong Ae; CASTRO, Matheus Augusto Araujo; EMBIRUCU, Emilia Katiane; STEINER, Carlos Eduardo; VAIRO, Filippo Pinto e; BALDO, Guilherme; GIUGLIANI, Roberto; POSWAR, Fabiano de OliveiraMucopolysaccharidosis type IIIB (MPS IIIB) is caused by deficiency of alpha-N-acetylglucosaminidase, leading to storage of heparan sulphate. The disease is characterized by intellectual disability and hyperactivity, among other neurological and somatic features. Here we studied retrospective data from a total of 19 MPS IIIB patients from Brazil, aiming to evaluate disease progression. Mean age at diagnosis was 7.2 years. Speech delay was one of the first symptoms to be identified, around 2-3 years of age. Behavioral alterations include hyperactivity and aggressiveness, starting around age four. By the end of the first decade, patients lost acquired abilities such as speech and ability to walk. Furthermore, as disease progresses, respiratory, cardiovascular and joint abnormalities were found in more than 50% of the patients, along with organomegaly. Most common cause of death was respiratory problems. The disease progression was characterized in multiple systems, and hopefully these data will help the design of appropriate clinical trials and clinical management guidelines.
- Pathogenic variants detected by RNA sequencing in Cornelia de Lange syndrome(2022) SEYAMA, Rie; UCHIYAMA, Yuri; CERONI, Jose Ricard Magliocco; KIM, Veronica Eun Hue; FURQUIM, Isabel; HONJO, Rachel Sayuri; CASTRO, Matheus Augusto Araujo; PIRES, Lucas Vieira Lacerda; AOI, Hiromi; IWAMA, Kazuhiro; HAMANAKA, Kohei; FUJITA, Atsushi; TSUCHIDA, Naomi; KOSHIMIZU, Eriko; MISAWA, Kazuharu; MIYATAKE, Satoko; MIZUGUCHI, Takeshi; MAKINO, Shintaro; ITAKURA, Atsuo; BERTOLA, Debora R.; KIM, Chong Ae; MATSUMOTO, NaomichiRecent studies suggest that transcript isoforms significantly overlap (approximately 60%) between brain tissue and Epstein-Barr virus-transformed lymphoblastoid cell lines (LCLs). Interestingly, 14 cohesion-related genes with variants that cause Cornelia de Lange Syndrome (CdLS) are highly expressed in the brain and LCLs. In this context, we first performed RNA sequencing of LCLs from 22 solved (with pathogenic variants) and 19 unsolved (with no confirmed variants) CdLS cases. Next, an RNA sequencing pipeline was developed using solved cases with two different methods: short variant analysis (for single-nucleotide and indel variants) and aberrant splicing detection analysis. Then, 19 unsolved cases were subsequently applied to our pipeline, and four pathogenic variants in NIPBL (one inframe deletion and three intronic variants) were newly identified. Two of three intronic variants were located at Alu elements in deep-intronic regions, creating cryptic exons. RNA sequencing with LCLs was useful for identifying hidden variants in exome-negative cases.
- Cerebellofaciodental syndrome in an adult patient: Expanding the phenotypic and natural history characteristics(2021) HONJO, Rachel Sayuri; CASTRO, Matheus Augusto Araujo; FERRACIOLLI, Suely Fazio; SOARES JUNIOR, Luiz Alberto Valente; PASTORINO, Antonio Carlos; BERTOLA, Debora Romeo; MIYAKE, Noriko; MATSUMOTO, Naomichi; KIM, Chong AeCerebellofaciodental syndrome is characterized by facial dysmorphisms, intellectual disability, cerebellar hypoplasia, and dental anomalies. It is an autosomal-recessive condition described in 2015 caused by pathogenic variants in BRF1. Here, we report a Brazilian patient who faced a diagnostic challenge beginning at 11 months of age. Fortunately, whole-exome sequencing (WES) was performed, detecting the BRF1 variants NM_001519.3:c.1649delG:p.(Gly550Alafs*36) and c.421C>T:p.(Arg141Cys) in compound heterozygosity, thus finally achieving a diagnosis of cerebellofaciodental syndrome. The patient is currently 25 years old and is the oldest patient yet reported. The clinical report and a review of published cases are presented. Atlanto-occipital fusion, a reduced foramen magnum and basilar invagination leading to compression of the medulla-spinal cord transition are skeletal findings not reported in previous cases. The description of syndromes with dental findings shows that such anomalies can be an important clue to relevant differential diagnoses. The cooperation of groups from different international centers made possible the resolution of this and other cases and is one of the strategies to bring medical advances to developing countries, where many patients with rare diseases are difficult to diagnose definitively.