Minigene splicing assessment of 20 novel synonymous and intronic glucokinase gene variants identified in patients with maturity‐onset diabetes of the young
| العنوان: | Minigene splicing assessment of 20 novel synonymous and intronic glucokinase gene variants identified in patients with maturity‐onset diabetes of the young |
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| المؤلفون: | Evgeny Vasilyev, Alena S Fedyaeva, Tatiana S Krasnova, Natalia A. Zubkova, Anatoly Tiulpakov, Petr M Rubtsov, Nina Makretskaya, Vasily Petrov, Anna I Melnikova |
| المصدر: | Human Mutation. 41:129-132 |
| بيانات النشر: | Hindawi Limited, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Adult, Male, Adolescent, Genotype, RNA Splicing, In silico, Biology, Maturity onset diabetes of the young, Young Adult, 03 medical and health sciences, Protein sequencing, Gene Frequency, Glucokinase, Genetics, medicine, Humans, Genetic Predisposition to Disease, In patient, Child, Gene, Alleles, Silent Mutation, Genetics (clinical), 030304 developmental biology, 0303 health sciences, 030305 genetics & heredity, Genetic Variation, High-Throughput Nucleotide Sequencing, Infant, Exons, medicine.disease, Introns, Amino Acid Substitution, Diabetes Mellitus, Type 2, Child, Preschool, Mutation, RNA splicing, Female, Chromosomes, Human, Pair 7, Minigene |
| الوصف: | 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. |
| تدمد: | 1098-1004 1059-7794 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cb7ee1deff99040eb88c7029223302f1 https://doi.org/10.1002/humu.23919 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....cb7ee1deff99040eb88c7029223302f1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10981004 10597794 |
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