論文 - 詳細
| RRC ID | 18231 |
|---|---|
| 著者 | Yoshimitsu M, Higuchi K, Miyata M, Devine S, Mattman A, Sirrs S, Medin JA, Tei C, Takenaka T. |
| タイトル | Identification of novel mutations in the α-galactosidase A gene in patients with Fabry disease: pitfalls of mutation analyses in patients with low α-galactosidase A activity. |
| ジャーナル | J Cardiol |
| Abstract |
BACKGROUND:Fabry disease is an X-linked lysosomal storage disorder caused by mutations of the α-galactosidase A (GLA) gene, and the disease is a relatively prevalent cause of left ventricular hypertrophy followed by conduction abnormalities and arrhythmias. Mutation analysis of the GLA gene is a valuable tool for accurate diagnosis of affected families. In this study, we carried out molecular studies of 10 unrelated families diagnosed with Fabry disease. MATERIALS AND METHODS:Genetic analysis of the GLA gene using conventional genomic sequencing was performed in 9 hemizygous males and 6 heterozygous females. In patients with no mutations in coding DNA sequence, multiplex ligation-dependent probe amplification (MLPA) and/or cDNA sequencing were performed. RESULTS:We identified a novel exon 2 deletion (IVS1_IVS2) in a heterozygous female by MLPA, which was undetectable by conventional sequencing methods. In addition, the g.9331G>A mutation that has previously been found only in patients with cardiac Fabry disease was found in 3 unrelated, newly-diagnosed, cardiac Fabry patients by sequencing GLA genomic DNA and cDNA. Two other novel mutations, g.8319A>G and 832delA were also found in addition to 4 previously reported mutations (R112C, C142Y, M296I, and G373D) in 6 other families. CONCLUSIONS:We could identify GLA gene mutations in all hemizygotes and heterozygotes from 10 families with Fabry disease. Mutations in 4 out of 10 families could not be identified by classical genomic analysis, which focuses on exons and the flanking region. Instead, these data suggest that MLPA analysis and cDNA sequence should be considered in genetic testing surveys of patients with Fabry disease. |
| 巻・号 | 57(3) |
| ページ | 345-53 |
| 公開日 | 2011-5-1 |
| DOI | 10.1016/j.jjcc.2010.12.004 |
| PII | S0914-5087(11)00007-4 |
| PMID | 21333496 |
| MeSH | Adult Aged Cardiomyopathy, Hypertrophic, Familial / complications DNA, Complementary / analysis Fabry Disease / genetics* Female Heterozygote Humans Male Middle Aged Mutation* Nucleic Acid Amplification Techniques RNA / isolation & purification Sequence Analysis, DNA alpha-Galactosidase / genetics* |
| IF | 2.246 |
| 引用数 | 11 |
| WOS 分野 | CARDIAC & CARDIOVASCULAR SYSTEMS |
| リソース情報 | |
| ヒト・動物細胞 | NHSF46(RCB0162) |