Utilizza questo identificativo per citare o creare un link a questo documento:
|Titolo:||Genetic and bioinformatics analysis of four novel GCK missense variants detected in Caucasian families with GCK-MODY phenotype.|
|Autori interni:||MALERBA, Giovanni|
Marin Vargas, Sergio Paul
|Data di pubblicazione:||2014|
|Abstract:||Heterozygous loss-of-function mutations in the glucokinase (GCK) gene cause maturity-onset diabetes of the young (MODY) subtype GCK (GCK-MODY/MODY2). GCK sequencing revealed 16 distinct mutations (13 missense, one nonsense, one splice site, and one frameshift-deletion) co-segregating with hyperglycaemia in 23 GCK-MODY families. Four missense substitutions (c.718A>G/p.Asn240Asp, c.757G>T/p.Val253Phe, c.872A>C/p.Lys291Thr, and c.1151C>T/p.Ala384Val) were novel and a founder effect for the nonsense mutation (c.76C>T/p.Gln26† ) was supposed. We tested whether an accurate bioinformatics approach could strengthen family-genetic evidence for missense variant pathogenicity in routine diagnostics, where wet-lab functional assays are generally unviable. In silico analyses of the novel missense variants, including orthologous sequence conservation, amino acid substitution (AAS)-pathogenicity predictors, structural modeling and splicing predictors, suggested that the AASs and/or the underlying nucleotide changes are likely to be pathogenic. This study shows how a careful bioinformatics analysis could provide effective suggestions to help molecular-genetic diagnosis in absence of wet-lab validations.|
|Appare nelle tipologie:||01.01 Articolo in Rivista|
File in questo prodotto:
Non ci sono file associati a questo prodotto.
- PubMed Central loading...
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.