Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Mais filtros

Base de dados
Ano de publicação
Tipo de documento
Intervalo de ano de publicação
1.
Hum Genomics ; 17(1): 102, 2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37968704

RESUMO

BACKGROUND: Next-generation sequencing has had a significant impact on genetic disease diagnosis, but the interpretation of the vast amount of genomic data it generates can be challenging. To address this, the American College of Medical Genetics and Genomics and the Association for Molecular Pathology have established guidelines for standardized variant interpretation. In this manuscript, we present the updated Hospital Israelita Albert Einstein Standards for Constitutional Sequence Variants Classification, incorporating modifications from leading genetics societies and the ClinGen initiative. RESULTS: First, we standardized the scientific publications, documents, and other reliable sources for this document to ensure an evidence-based approach. Next, we defined the databases that would provide variant information for the classification process, established the terminology for molecular findings, set standards for disease-gene associations, and determined the nomenclature for classification criteria. Subsequently, we defined the general rules for variant classification and the Bayesian statistical reasoning principles to enhance this process. We also defined bioinformatics standards for automated classification. Our workgroup adhered to gene-specific rules and workflows curated by the ClinGen Variant Curation Expert Panels whenever available. Additionally, a distinct set of specifications for criteria modulation was created for cancer genes, recognizing their unique characteristics. CONCLUSIONS: The development of an internal consensus and standards for constitutional sequence variant classification, specifically adapted to the Brazilian population, further contributes to the continuous refinement of variant classification practices. The aim of these efforts from the workgroup is to enhance the reliability and uniformity of variant classification.


Assuntos
Testes Genéticos , Variação Genética , Humanos , Estados Unidos , Mutação , Reprodutibilidade dos Testes , Teorema de Bayes , Genoma Humano
2.
Am J Med Genet A ; 185(4): 1047-1058, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33381921

RESUMO

We aim to characterize patients with Gomez-López-Hernández syndrome (GLHS) clinically and to investigate them molecularly. A clinical protocol, including a morphological and neuropsychological assessment, was applied to 13 patients with GLHS. Single-nucleotide polymorphism (SNP) array and whole-exome sequencing were undertaken; magnetic resonance imaging was performed in 12 patients, including high-resolution, heavily T2-weighted sequences (HRT2) in 6 patients to analyze the trigeminal nerves. All patients presented alopecia; two did not present rhombencephalosynapsis (RES); trigeminal anesthesia was present in 5 of the 11 patients (45.4%); brachycephaly/brachyturricephaly and mid-face retrusion were found in 84.6 and 92.3% of the patients, respectively. One patient had intellectual disability. HRT2 sequences showed trigeminal nerve hypoplasia in four of the six patients; all four had clinical signs of trigeminal anesthesia. No common candidate gene was found to explain GLHS phenotype. RES does not seem to be an obligatory finding in respect of GLHS diagnosis. We propose that a diagnosis of GLHS should be considered in patients with at least two of the following criteria: focal non-scarring alopecia, rhombencephalosynapsis, craniofacial anomalies (brachyturrycephaly, brachycephaly or mid-face retrusion), trigeminal anesthesia or anatomic abnormalities of the trigeminal nerve. Studies focusing on germline whole genome sequencing or DNA and/or RNA sequencing of the alopecia tissue may be the next step for the better understanding of GLHS etiology.


Assuntos
Anormalidades Múltiplas/genética , Fosfatase Ácida/genética , Alopecia/genética , Cerebelo/anormalidades , Anormalidades Craniofaciais/genética , Sequenciamento do Exoma , Transtornos do Crescimento/genética , Síndromes Neurocutâneas/genética , Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/diagnóstico por imagem , Anormalidades Múltiplas/patologia , Adolescente , Adulto , Alopecia/diagnóstico , Alopecia/diagnóstico por imagem , Alopecia/patologia , Brasil/epidemiologia , Cerebelo/diagnóstico por imagem , Cerebelo/patologia , Criança , Pré-Escolar , Anormalidades Craniofaciais/diagnóstico , Anormalidades Craniofaciais/diagnóstico por imagem , Anormalidades Craniofaciais/patologia , Feminino , Transtornos do Crescimento/diagnóstico , Transtornos do Crescimento/diagnóstico por imagem , Transtornos do Crescimento/patologia , Humanos , Lactente , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Síndromes Neurocutâneas/diagnóstico , Síndromes Neurocutâneas/diagnóstico por imagem , Síndromes Neurocutâneas/patologia , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Rombencéfalo/diagnóstico por imagem , Rombencéfalo/patologia , Nervo Trigêmeo/diagnóstico por imagem , Nervo Trigêmeo/metabolismo , Nervo Trigêmeo/patologia , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA