Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 5 de 5
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Genet Med ; 23(8): 1574-1577, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33927379

RESUMO

PURPOSE: Recent evolution of sequencing technologies and the development of international standards in variant interpretation have profoundly changed the diagnostic approaches in clinical genetics. As a consequence, many variants that were initially claimed to be disease-causing can be now reclassified as benign or uncertain in light of the new data available. Unfortunately, the misclassified variants are still present in the scientific literature and variant databases, greatly interfering with interpretation of diagnostic sequencing results. Despite the urgent need, large-scale efforts to update the classifications of these variants are still not sufficient. METHODS: We retrospectively analyzed 176 DYSF gene variants that were identified in dysferlinopathy patients referred to the Marseille Medical Genetics Department for diagnostic sequencing since 2001. RESULTS: We reclassified all variants into five-tier American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) pathogenicity classes, revealing changed pathogenicity for 17 variants. We then updated the information for the variants that have been previously published in the variant database and submitted 46 additional DYSF variants. CONCLUSION: Besides direct benefit for dysferlinopathy diagnostics, our study contributes to the much needed effort to reanalyze variants from previously published cohorts and to work with curators of variant databases to update the entries for erroneously classified variants.


Assuntos
Variação Genética , Distrofia Muscular do Cíngulo dos Membros , Disferlina/genética , Testes Genéticos , Variação Genética/genética , Humanos , Estudos Retrospectivos
3.
Orphanet J Rare Dis ; 14(1): 288, 2019 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-31829210

RESUMO

BACKGROUND: Segmental progeroid syndromes are a heterogeneous group of rare and often severe genetic disorders that have been studied since the twentieth century. These progeroid syndromes are defined as segmental because only some of the features observed during natural aging are accelerated. METHODS: Since 2015, the Molecular Genetics Laboratory in Marseille La Timone Hospital proposes molecular diagnosis of premature aging syndromes including laminopathies and related disorders upon NGS sequencing of a panel of 82 genes involved in these syndromes. We analyzed the results obtained in 4 years on 66 patients issued from France and abroad. RESULTS: Globally, pathogenic or likely pathogenic variants (ACMG class 5 or 4) were identified in about 1/4 of the cases; among these, 9 pathogenic variants were novel. On the other hand, the diagnostic yield of our panel was over 60% when the patients were addressed upon a nosologically specific clinical suspicion, excepted for connective tissue disorders, for which clinical diagnosis may be more challenging. Prenatal testing was proposed to 3 families. We additionally detected 16 variants of uncertain significance and reclassified 3 of them as benign upon segregation analysis in first degree relatives. CONCLUSIONS: High throughput sequencing using the Laminopathies/ Premature Aging disorders panel allowed molecular diagnosis of rare disorders associated with premature aging features and genetic counseling for families, representing an interesting first-level analysis before whole genome sequencing may be proposed, as a future second step, by the National high throughput sequencing platforms ("Medicine France Genomics 2025" Plan), in families without molecular diagnosis.


Assuntos
Senilidade Prematura/genética , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Aconselhamento Genético , Testes Genéticos , Variação Genética/genética , Genômica/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Mutação/genética , Análise de Sequência de DNA/métodos , Sequenciamento Completo do Genoma/métodos , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...