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

Base de dados
País/Região como assunto
Ano de publicação
Tipo de documento
Assunto da revista
País de afiliação
Intervalo de ano de publicação
1.
Hum Mutat ; 41(1): 115-121, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31469207

RESUMO

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disease of motile cilia. Even though PCD is widely studied, North-African patients have been rarely explored. In this study, we aim at confirming the clinical diagnosis and explore the genetic spectrum of PCD in a cohort of Tunisian patients. Forty clinically diagnosed patients with PCD belonging to 34 families were recruited from Tunisian pediatric departments. In each proband, targeted capture PCD panel sequencing of the 40 PCD genes was performed. PCD panel sequencing identified bi-allelic mutations in 82% of the families in eight PCD genes. Remarkably, 23.5% of patients carried the same c.2190del CCDC39 mutation. Single nucleotide polymorphism profiling in six unrelated patients carrying this mutation has revealed a founder effect in North-African patients. This mutation is estimated to date back at least 1,400-1,750 years ago. The identification of this major allele allowed us to suggest a cost-effective genetic diagnostic strategy in North-African patients with PCD.


Assuntos
Dineínas/genética , Predisposição Genética para Doença , Síndrome de Kartagener/epidemiologia , Síndrome de Kartagener/genética , Mutação , Vigilância da População , Alelos , Substituição de Aminoácidos , Éxons , Feminino , Genótipo , Humanos , Síndrome de Kartagener/diagnóstico , Masculino , Tunísia/epidemiologia
2.
Hum Mutat ; 40(11): 2033-2043, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31231873

RESUMO

Isolated growth hormone deficiency (IGHD) is a rare condition mainly caused by mutations in GH1. The aim of this study was to assess the contribution of GHRHR mutations to IGHD in an unusually large group of patients. All GHRHR coding exons and flanking intronic regions were sequenced in 312 unrelated patients with nonsyndromic IGHD. Functional consequences of all newly identified missense variants were assessed in vitro (i.e., study of the expression of recombinant GHRHRs and their ability to activate the cyclic adenosine monophosphate (cAMP) signaling pathway). Genotype-phenotype correlation analyses were performed according to the nature of the identified mutation. We identified 20 different disease-causing GHRHR mutations (truncating and missense loss-of-function mutations), among which 15 are novel, in 24 unrelated patients. Of note, about half (13/24) of those patients represent sporadic cases. The clinical phenotype of patients with at least one missense GHRHR mutation was found to be indistinguishable from that of patients with bi-allelic truncating mutations. This study, which unveils disease-causing GHRHR mutations in 8% (24/312) of IGHD cases, identifies GHRHR as the second IGHD gene most frequently involved after GH1. The finding that 8% of IGHD cases without GH1 mutations are explained by GHRHR molecular defects (including missense mutations), together with the high proportion of sporadic cases among those patients, has important implications for genetic counseling.


Assuntos
Nanismo Hipofisário/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Mutação , Receptores de Neuropeptídeos/genética , Receptores de Hormônios Reguladores de Hormônio Hipofisário/genética , Alelos , Sequência de Aminoácidos , Substituição de Aminoácidos , AMP Cíclico , Análise Mutacional de DNA , Nanismo Hipofisário/diagnóstico , Feminino , Genótipo , Hormônio do Crescimento Humano/genética , Humanos , Masculino , Linhagem , Receptores de Neuropeptídeos/química , Receptores de Hormônios Reguladores de Hormônio Hipofisário/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA