Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 1 de 1
Filter
Add more filters










Database
Language
Publication year range
1.
Mol Biol (Mosk) ; 48(2): 288-94, 2014.
Article in Russian | MEDLINE | ID: mdl-25850297

ABSTRACT

Two novel mutations in glucokinase (GCK) gene-G to C substitution at -1 position of intron 7 acceptor splice site (c. 864-1G>C) and synonymous substitution c. 666C>G (GTC>GTG, p.V222V) in exon 6--were identified in patients with monogenic diabetes MODY2 (Maturity Onset Diabetes of Young). GCK minigenes with these mutations were constructed. Analysis of splicing products upon transfection of minigenes into human embryonic cell line HEK293 has shown that each of these nucleotide substitutions impair normal splicing. Mutation c.864-1G>C blocks the usage of normal acceptor site which activates cryptic acceptor splice sites within intron 7 and generates aberrant RNAs containing the portions ofintron 7. Synonymous substitution c.666C>G creates novel donor splice site in exon 6 that leads to formation of defective GCK mRNA with deletion of 16 nucleotides of exon 6. Analysis of in vitro splicing of minigenes confirms the inactivating action of novel mutations on glucokinase expression.


Subject(s)
Alternative Splicing , Diabetes Mellitus, Type 2/genetics , Glucokinase/genetics , Mutation , Nonsense Mediated mRNA Decay , Adolescent , Base Sequence , Diabetes Mellitus, Type 2/pathology , Exons , Gene Expression , HEK293 Cells , Humans , Introns , Molecular Sequence Data , Sequence Analysis, DNA , Sequence Deletion , Young Adult
SELECTION OF CITATIONS
SEARCH DETAIL
...