Novel mutations of the FANCG gene causing alternative splicing in Japanese Fanconi anemia
| Autor: | Masao S. Sasaki, Hideo Mugishima, Takashi Shimizu, Toshiko Yamada, Mariko Okubo, Akira Tachibana |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
FANCG Gene
Fanconi anemia complementation group C DNA Mutational Analysis Nonsense mutation Biology Exon Japan Fanconi anemia FANCG Genetics medicine Humans Fanconi Anemia Complementation Group G Protein Genetics (clinical) Family Health Alternative splicing FANCC Gene medicine.disease Molecular biology Pedigree DNA-Binding Proteins Alternative Splicing Fanconi Anemia Amino Acid Substitution Mutation |
| Zdroj: | Journal of Human Genetics. 45:159-166 |
| ISSN: | 1435-232X 1434-5161 |
| Popis: | Fanconi anemia (FA), an autosomal recessive disorder characterized by a progressive pancytopenia associated with congenital anomalies and high predisposition to malignancies, is a genetically and clinically heterogeneous disease. At least eight complementation groups (FA-A to FA-H) have been identified. Previously, we studied mutations of the FANCA gene, responsible for FA-A, and found pathogenic mutations in 12 of 15 unclassified Japanese FA patients. Here, we further studied an additional 5 FA patients for sequence alterations of the FANCA gene and found pathogenic mutations in 2 of them. We further analyzed mutations of the FANCC and FANCG genes, responsible for FA-C and FA-G, respectively, in the remaining 6 FA patients. Although there was no alterations in the FANCC gene in these 6 patients, two novel mutations of the FANCG gene, causing aberrant RNA splicing, were detected in 2 FA patients. One was a base substitution from G to C of the invariant GT dinucleotides at the splice donor site of intron 3, resulting in the skipping of exon 3, as well as the skipping of exons 3 and 4. The other was a base substitution from C to T in exon 8, creating a nonsense codon (Q356X). This mutation resulted in the exclusion of a sequence of 18 nucleotides containing the mutation from the mRNA, without affecting the splicing potential of either the authentic or the cryptic splice donor site. Collectively, 14 of the 20 unclassified Japanese FA patients belong to the FA-A group, 2 belong to the FA-G group, and none belongs to the FA-C group. |
| Databáze: | OpenAIRE |
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