MATHEUS AUGUSTO ARAUJO CASTRO

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4
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Instituto da Criança, Hospital das Clínicas, Faculdade de Medicina - Médico
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico

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Colaboração internacional: Estados Unidos ×

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Agora exibindo 1 - 4 de 4
  • article 5 Citação(ões) na Scopus
    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, Marwan
    Primary 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.
  • article 0 Citação(ões) na Scopus
    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 Oliveira
    Mucopolysaccharidosis 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.
  • article 1 Citação(ões) na Scopus
    Biallelic variants in DNA2 cause poikiloderma with congenital cataracts and severe growth failure reminiscent of Rothmund-Thomson syndrome
    (2023) LAZZARO FILHO, Ricardo Di; YAMAMOTO, Guilherme Lopes; SILVA, Tiago J.; ROCHA, Leticia A.; LINNENKAMP, Bianca D. W.; CASTRO, Matheus Augusto Araujo; BARTHOLDI, Deborah; SCHALLER, Andre; LEEB, Tosso; KELMANN, Samantha; UTAGAWA, Claudia Y.; STEINER, Carlos E.; STEINMETZ, Leandra; HONJO, Rachel Sayuri; KIM, Chong Ae; WANG, Lisa; ABOURJAILI-BILODEAU, Raphael; CAMPEAU, Philippe; WARMAN, Matthew; PASSOS-BUENO, Maria Rita; HOCH, Nicolas C.; BERTOLA, Debora Romeo
    Rothmund-Thomson syndrome (RTS) is a rare, heterogeneous autosomal recessive genodermatosis, with poikiloderma as its hallmark. It is classified into two types: type I, with biallelic variants in ANAPC1 and juvenile cataracts, and type II, with biallelic variants in RECQL4, increased cancer risk and no cataracts. We report on six Brazilian probands and two siblings of Swiss/Portuguese ancestry presenting with severe short stature, widespread poikiloderma and congenital ocular anomalies. Genomic and functional analysis revealed compound heterozygosis for a deep intronic splicing variant in trans with loss of function variants in DNA2, with reduction of the protein levels and impaired DNA double-strand break repair. The intronic variant is shared by all patients, as well as the Portuguese father of the European siblings, indicating a probable founder effect. Biallelic variants in DNA2 were previously associated with microcephalic osteodysplastic primordial dwarfism. Although the individuals reported here present a similar growth pattern, the presence of poikiloderma and ocular anomalies is unique. Thus, we have broadened the phenotypical spectrum of DNA2 mutations, incorporating clinical characteristics of RTS. Although a clear genotype-phenotype correlation cannot be definitively established at this moment, we speculate that the residual activity of the splicing variant allele could be responsible for the distinct manifestations of DNA2-related syndromes.
  • article 1 Citação(ões) na Scopus
    Twenty-year follow-up of the facial phenotype of Brazilian patients with Sotos syndrome
    (2021) CASTRO, Matheus Augusto Araujo; SANTOS, Juliana Heather Vedovato dos; HONJO, Rachel Sayuri; YAMAMOTO, Guilherme Lopes; BERTOLA, Debora Romeo; HURST, Anna C.; CHORICH, Lynn P.; LAYMAN, Lawrence C.; KIM, Chong Ae; KIM, Hyung-Goo
    Sotos syndrome is characterized by overgrowth starting before birth through childhood with intellectual disability and craniofacial anomalies. The majority of patients are large for gestational age with developmental delay or intellectual disability. The majority of cases are caused by pathogenic variants in NSD1. The most consistent physical features in this disorder are facial dysmorphisms including prominent forehead, downslanted palpebral fissures, prognathism with a pointed chin, and a long and narrow face. We present a follow-up to a cohort of 11 individuals found to harbor heterozygous, pathogenic, or likely pathogenic variants in NSD1. We analyzed the facial dysmorphisms and the condition using retrospective over 20 years. Among these patients, followed in our medical genetics outpatient clinic for variable periods of time, all had a phenotype compatible with the characteristic Sotos syndrome facial features, which evolved with time and became superimposed with natural aging modifications. We present here a long-term follow-up of facial features of Brazilian patients with molecularly confirmed Sotos syndrome. In this largest Brazilian cohort of molecularly confirmed patients with Sotos syndrome to date, we provide a careful description of the facial phenotype, which becomes less pronounced with aging and possibly more difficult to recognize in adults. These results may have broad clinical implications for diagnosis and add to the global clinical delineation of this condition.