Identification of novel mutations in Arabs with cystic fibrosis and their impact on the cystic fibrosis transmembrane regulator mutation detection rate in Arab populations
| Autor: | H Nazer, H Banjar, M H Al-Hamed, B F Meyer, I Moggari, M Kambouris |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities Cystic Fibrosis Cystic Fibrosis Transmembrane Conductance Regulator Heteroduplex Analysis Biology medicine.disease_cause Polymerase Chain Reaction Cystic fibrosis Frameshift mutation Exon medicine Humans Point Mutation Frameshift Mutation ΔF508 Alleles Genetics Mutation Splice site mutation Point mutation Exons Sequence Analysis DNA medicine.disease Cystic fibrosis transmembrane conductance regulator Arabs Pediatrics Perinatology and Child Health biology.protein |
| Zdroj: | European Journal of Pediatrics. 159:303-309 |
| ISSN: | 1432-1076 0340-6199 |
| Popis: | The cystic fibrosis transmembrane regulator (CFTR) gene in Arab patients with cystic fibrosis (CF) (sweat chloride >60 mmol/l) from 61 unrelated families was screened for mutations in exons 3, 4, 5, 7, 10, 11, 16 and 19 and for mutations W1282X, N1303K and 3849 + 10kbC → T. Eight novel mutations were identified. These are: in exon 4: a) 425del42 (an in-frame 42 bp deletion that removes 14 amino acids and causes Gln98 → His at the point of deletion), b) 475G → T (Glu115 → Stop) and c) 548A → T (His139 → Leu); in intron 5, 711 + 1G → A (splice site mutation); in exon 10, 1548delG (deletion of a “G” nucleotide causing a frameshift mutation that alters the amino acid sequence at residue 473 and results in translation termination at residue 526); in exon 11, a) 1729T → C (Ph533E → Leu) and b) 1811 + 2 (splice site mutation) and finally in exon 19, 3361A → T (Lys1177 → Stop). All mutations were detected by heteroduplex analysis and identified by sequencing. Of more than 850 known CFTR mutations, only 9 were encountered. The comparative frequencies of the most common mutations are: 1548delG> I123V=ΔF508=3120 + 1G → A > H139L. Screening for these five mutations identifies 60% of the CF alleles in Arab populations. The novel mutation 1548delG is the most frequent (17%) among Arabs. Conclusion Novel Arab-specific mutations were identified in the CFTR gene underlying cystic fibrosis. As a result of this study, the CFTR mutation detection rate among Arabs with cystic fibrosis is now comparable to that of other populations. |
| Databáze: | OpenAIRE |
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