Minigene splicing assessment of 20 novel synonymous and intronic glucokinase gene variants identified in patients with maturity-onset diabetes of the young.
Hum Mutat
; 41(1): 129-132, 2020 01.
Article
em En
| MEDLINE
| ID: mdl-31529753
ABSTRACT
The next-generation sequencing (NGS) has become a routine method for diagnostics of inherited disorders. However, assessment of the discovered variants may be challenging, especially when they are not predicted to change the protein sequence. Here we performed a functional analysis of 20 novel or rare intronic and synonymous glucokinase (GCK) gene variants identified by targeted NGS in 1,130 patients with maturity-onset diabetes of the young. Human Splicing Finder, ver 3.1 and a precomputed index of splicing variants (SPIDEX) were used for in silico prediction. In vitro effects of GCK gene variants on splicing were tested using a minigene expression approach. In vitro effect on splicing was shown for 9 of 20 variants, including two synonymous substitutions. In silico and in vitro results matched in about 50% of cases. The results demonstrate that novel or rare apparently benign GCK gene variants should be regarded as potential splicing mutations.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Variação Genética
/
Íntrons
/
Splicing de RNA
/
Predisposição Genética para Doença
/
Diabetes Mellitus Tipo 2
/
Mutação Silenciosa
/
Glucoquinase
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Adolescent
/
Adult
/
Child
/
Child, preschool
/
Female
/
Humans
/
Infant
/
Male
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article