Síndrome de excesso aparente de mineralocorticóide em um menino brasileiro causada pela mutação p.R186C em homozigose no gene HSD11B2

The apparent mineralocorticoid excess syndrome (AME) is a rare autosomal recessive disorder due to the deficiency of 11β-hydroxysteroid dehydrogenase type 2 enzyme (11beta-HSD2). The 11beta-HSD2 enzyme, encoded by HSD11B2 gene, metabolizes active cortisol in cortisone. Mutations on HSD11B2 gene affect the enzyme activity by leading to an excess of cortisol, which causes its inappropriate access to mineralocorticoid receptor. Therefore, cortisol will bind mineralocorticoid receptor. The human HSD11B2 gene maps to chromosome 16q22 and consists of five exons encoding a protein of 405 amino acids. We present here clinical and molecular studies on a Brazilian boy who was born pre-term after an oligodramnious pregnancy. He was diagnosed as having AME at the age of 26 months. His parents are second cousins. Molecular characterization of the HSD11B2 gene revealed the homozygous mutation p.R186C. The patient described here is the second case of HDS11B2 gene mutation reported in Brazilian patients with AME.A síndrome de excesso aparente de mineralocorticóide (AME) é uma doença autossômica recessiva rara devido à deficiência da enzima 11β-hidroxiesterσide desidrogenase tipo 2 (11beta-HSD2). A enzima 11beta-HSD2 metaboliza o cortisol ativo a cortisona. As mutações no gene HSD11B2, que codifica a enzima, afetam sua atividade levando a um excesso de cortisol, que terá acesso inapropriado ao receptor de mineralocorticóide, competindo com a ligação da aldosterona. O gene HDS11B2 humano está localizado no cromossomo 16q22 e é formado por 5 éxons que codificam uma proteína de 405 aminoácidos. Este relato apresenta os estudos clínicos e moleculares de um paciente brasileiro do sexo masculino que nasceu prematuro depois de uma gestação sob oligodrâmnio. Recebeu o diagnóstico de AME com 26 meses de idade. Seus pais são primos em segundo grau. A caracterização molecular do gene HSD11B2 revelou a mutação p.R186C em homozigose. O paciente descrito é o segundo caso relatado de brasileiro com mutação no gene HSD11B2.12771281Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Apparent Mineralocorticoid Excess Syndrome In A Brazilian Boy Caused By The Homozygous Missense Mutation P.r186c In The Hsd11b2 Gene.

The apparent mineralocorticoid excess syndrome (AME) is a rare autosomal recessive disorder due to the deficiency of 11beta-hydroxysteroid dehydrogenase type 2 enzyme (11beta-HSD2). The 11beta-HSD2 enzyme, encoded by HSD11B2 gene, metabolizes active cortisol in cortisone. Mutations on HSD11B2 gene affect the enzyme activity by leading to an excess of cortisol, which causes its inappropriate access to mineralocorticoid receptor. Therefore, cortisol will bind mineralocorticoid receptor. The human HSD11B2 gene maps to chromosome 16q22 and consists of five exons encoding a protein of 405 amino acids. We present here clinical and molecular studies on a Brazilian boy who was born pre-term after an oligodramnious pregnancy. He was diagnosed as having AME at the age of 26 months. His parents are second cousins. Molecular characterization of the HSD11B2 gene revealed the homozygous mutation p.R186C. The patient described here is the second case of HDS11B2 gene mutation reported in Brazilian patients with AME.521277-8

[5alpha-reductase Type 2 Deficiency: Experiences From Campinas (sp) And Salvador (ba)].

To report the experience regarding patients with steroid 5alpha-reductase type 2 deficiency from three different clinical services in Brazil. Twenty five patients with clinical and hormonal features of 5alpha-reductase deficiency from 23 families (15 from Bahia, 7 from São Paulo and 1 from Minas Gerais) were included in this study. Clinical, hormonal and molecular data were evaluated. The molecular analysis of the five exons of the SRD5A2 gene was done by automatic or manual sequencing of PCR products. In ten families, SRD5A2 mutations were found in homozygosis (5 with G183S, 2 with R246W, 1 with G196S, 1 with del642T, 1 with 217_218insC), in three in compound heterozygosis (1 with Q126R/IVS3+1G>A, 1 with Q126R/del418T, 1 with Q126R/G158R) while other three were heterozygous, with only one deleterious mutation (1 with G196S, 1 with A207D, and 1 with R246W). In seven cases, no sequencing abnormalities were detected. The G183S substitution was the most frequently found among miscegenated patients (Afro-Euro-Brazilians) from Bahia. Hormonal and clinical findings did not differ between patients with or without mutations, exception made to a higher frequency of consanguinity and greater severity of genital ambiguity in the first group. Our results reinforce the importance of molecular investigation for the diagnosis of this disease and point out to the finding of a very frequent mutation (G183S) in our series, especially in patients with mixed ethnic background from Bahia, and the description of mutations that have only been reported in Brazilian patients so far.49103-1

46,xx Dsd And Antley-bixler Syndrome Due To Novel Mutations In The Cytochrome P450 Oxidoreductase Gene.

Deficiency of the enzyme P450 oxidoreductase is a rare form of congenital adrenal hyperplasia with characteristics of combined and partial impairments in steroidogenic enzyme activities, as P450 oxidoreductase transfers electrons to CYP21A2, CYP17A1, and CYP19A1. It results in disorders of sex development and skeletal malformations similar to Antley-Bixley syndrome. We report the case of a 9-year-old girl who was born with virilized genitalia (Prader stage V), absence of palpable gonads, 46,XX karyotype, and hypergonadotropic hypogonadism. During the first year of life, ovarian cyst, partial adrenal insufficiency, and osteoarticular changes, such as mild craniosynostosis, carpal and tarsal synostosis, and limited forearm pronosupination were observed. Her mother presented severe virilization during pregnancy. The molecular analysis of P450 oxidoreductase gene revealed compound heterozygosis for the nonsense p.Arg223*, and the novel missense p.Met408Lys, inherited from the father and the mother, respectively.56578-8

Large scale genome-centric metagenomic data from the gut microbiome of food-producing animals and humans

Bill & Melinda Gates Foundation [INV-00764] and CNPq/DECIT [443805/2018-0]; Fundação Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio De Janeiro (FAPERJ) E-26/201.046/2022; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ) 307145/2021-2; 312066/2019-8 Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)National Laboratory of Scientific Computing. Bioinformatics Laboratory. Rio de Janeiro, RJ, BrazilNational Laboratory of Scientific Computing. Bioinformatics Laboratory. Rio de Janeiro, RJ, BrazilUniversidade Federal de São Paulo. Escola Paulista de Medicina. Department of Internal Medicine. Division of Infectious Diseases. Laboratório Alerta. São Paulo, SP, BrazilUniversidade Federal de São Paulo. Escola Paulista de Medicina. Department of Internal Medicine. Division of Infectious Diseases. Laboratório Alerta. São Paulo, SP, BrazilUniversidade Federal de São Paulo. Escola Paulista de Medicina. Department of Internal Medicine. Division of Infectious Diseases. Laboratório Alerta. São Paulo, SP, BrazilRegional University of Blumenau. Blumenau, SC, BrazilNational Laboratory of Scientific Computing. Bioinformatics Laboratory. Rio de Janeiro, RJ, BrazilNational Laboratory of Scientific Computing. Bioinformatics Laboratory. Rio de Janeiro, RJ, BrazilMinistério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, BrasilMinistério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, BrasilFederal University of Ceará. Postgraduate Program in Medical Microbiology. Group of Applied Medical Microbiology. Fortaleza, CE, Brazil.Regional University of Blumenau. Blumenau, SC, Brazil.Universidade Federal de São Paulo. Escola Paulista de Medicina. Department of Internal Medicine. Division of Infectious Diseases. Laboratório Alerta. São Paulo, SP, Brazil / Universidade Federal de São Paulo. Instituto de Ciências Ambientais, Químicas e Farmacêuticas. Departamento de Ciências Biológicas. Laboratório de Imunologia e Bacteriologia. Setor de Biologia Molecular, Microbiologia e Imunologia. Diadema, SP, BrazilFederal University of Ceará. Postgraduate Program in Medical Microbiology. Group of Applied Medical Microbiology. Fortaleza, CE, Brazil.Universidade Federal da Grande Dourados. Laboratório de Pesquisa em Ciências da Saúde. Dourados, MS, BrazilUniversity São Francisco. Laboratory of Molecular Biology of Microorganisms. Bragança Paulista, SP, BrazilMinistério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, BrasilUniversidade Federal da Grande Dourados. Laboratório de Pesquisa em Ciências da Saúde. Dourados, MS, BrazilUniversidade Federal de São Paulo. Escola Paulista de Medicina. Department of Internal Medicine. Division of Infectious Diseases. Laboratório Alerta. São Paulo, SP, BrazilUniversidade Federal de São Paulo. Escola Paulista de Medicina. Department of Internal Medicine. Division of Infectious Diseases. Laboratório Alerta. São Paulo, SP, BrazilUniversidade Federal da Grande Dourados. Laboratório de Pesquisa em Ciências da Saúde. Dourados, MS, BrazilUniversity São Francisco. Laboratory of Molecular Biology of Microorganisms. Bragança Paulista, SP, BrazilMinistério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, BrasilUniversidade Federal de São Paulo. Escola Paulista de Medicina. Department of Internal Medicine. Division of Infectious Diseases. Laboratório Especial de Microbiologia Clínica. São Paulo, SP, BrazilUniversidade Federal de São Paulo. Escola Paulista de Medicina. Department of Internal Medicine. Division of Infectious Diseases. Laboratório Alerta. São Paulo, SP, Brazil / Universidade Federal de São Paulo. Instituto de Ciências Ambientais, Químicas e Farmacêuticas. Departamento de Ciências Biológicas. Laboratório de Imunologia e Bacteriologia. Setor de Biologia Molecular, Microbiologia e Imunologia. Diadema, SP, Brazil.Universidade Federal de São Paulo. Escola Paulista de Medicina. Department of Internal Medicine. Division of Infectious Diseases. Laboratório Alerta. São Paulo, SP, Brazil / Universidade Federal de São Paulo. Escola Paulista de Medicina. Department of Internal Medicine. Division of Infectious Diseases. Laboratório Especial de Microbiologia Clínica. São Paulo, SP, BrazilNational Laboratory of Scientific Computing. Bioinformatics Laboratory. Rio de Janeiro, RJ, BrazilThe One Health concept is a global strategy to study the relationship between human and animal health and the transfer of pathogenic and non-pathogenic species between these systems. However, to the best of our knowledge, no data based on One Health genome-centric metagenomics are available in public repositories. Here, we present a dataset based on a pilot-study of 2,915 metagenome-assembled genomes (MAGs) of 107 samples from the human (N = 34), cattle (N = 28), swine (N = 15) and poultry (N = 30) gut microbiomes. Samples were collected from the five Brazilian geographical regions. Of the draft genomes, 1,273 were high-quality drafts (>= 90% of completeness and = 50% of completeness and <= 10% of contamination). Taxonomic predictions were based on the alignment and concatenation of single-marker genes, and the most representative phyla were Bacteroidota, Firmicutes, and Proteobacteria. Many of these species represent potential pathogens that have already been described or potential new families, genera, and species with potential biotechnological applications. Analyses of this dataset will highlight discoveries about the ecology and functional role of pathogens and uncultivated Archaea and Bacteria from food-producing animals and humans. Furthermore, it also represents an opportunity to describe new species from underrepresented taxonomic groups