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

Base de dados
Ano de publicação
Tipo de documento
Intervalo de ano de publicação
1.
Hum Mutat ; 38(7): 764-777, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28432734

RESUMO

We developed a variant database for diabetes syndrome genes, using the Leiden Open Variation Database platform, containing observed phenotypes matched to the genetic variations. We populated it with 628 published disease-associated variants (December 2016) for: WFS1 (n = 309), CISD2 (n = 3), ALMS1 (n = 268), and SLC19A2 (n = 48) for Wolfram type 1, Wolfram type 2, Alström, and Thiamine-responsive megaloblastic anemia syndromes, respectively; and included 23 previously unpublished novel germline variants in WFS1 and 17 variants in ALMS1. We then investigated genotype-phenotype relations for the WFS1 gene. The presence of biallelic loss-of-function variants predicted Wolfram syndrome defined by insulin-dependent diabetes and optic atrophy, with a sensitivity of 79% (95% CI 75%-83%) and specificity of 92% (83%-97%). The presence of minor loss-of-function variants in WFS1 predicted isolated diabetes, isolated deafness, or isolated congenital cataracts without development of the full syndrome (sensitivity 100% [93%-100%]; specificity 78% [73%-82%]). The ability to provide a prognostic prediction based on genotype will lead to improvements in patient care and counseling. The development of the database as a repository for monogenic diabetes gene variants will allow prognostic predictions for other diabetes syndromes as next-generation sequencing expands the repertoire of genotypes and phenotypes. The database is publicly available online at https://lovd.euro-wabb.org.


Assuntos
Anemia Megaloblástica/genética , Bases de Dados Genéticas , Diabetes Mellitus/genética , Perda Auditiva Neurossensorial/genética , Deficiência de Tiamina/congênito , Síndrome de Wolfram/genética , Adolescente , Adulto , Criança , Pré-Escolar , Éxons , Saúde da Família , Feminino , Estudos de Associação Genética , Variação Genética , Genótipo , Homozigoto , Humanos , Masculino , Fenótipo , Prognóstico , Sensibilidade e Especificidade , Deficiência de Tiamina/genética , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA