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
3 resultados
Resultados de Busca
Agora exibindo 1 - 3 de 3
- 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
- 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 RomeoRothmund-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.