The novel complex allele [A238V;F508del] of the CFTR gene: clinical phenotype and possible implications for cystic fibrosis etiological therapies
| Autor: | Luigi Ratclif, Crescenzio Gallo, Teresa Santostasi, Maria Giuseppina Pantaleo, Anna Diana, Antonio Manca, Angela Polizzi, Giuseppina Leonetti, Massimo Conese, Danila Rosa Iusco |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Cystic Fibrosis DNA Mutational Analysis Cystic Fibrosis Transmembrane Conductance Regulator 030105 genetics & heredity Compound heterozygosity Cystic fibrosis Gastroenterology 03 medical and health sciences Chlorides Internal medicine Molecular genetics Genetics medicine Humans Allele Child Codon Allele frequency Alleles Genetics (clinical) Sequence Deletion biology Homozygote Infant Newborn Infant Bacterial Infections Prognosis medicine.disease Molecular biology Cystic fibrosis transmembrane conductance regulator Respiratory Function Tests C-Reactive Protein Phenotype 030104 developmental biology Amino Acid Substitution Statistical genetics Child Preschool Mutation (genetic algorithm) biology.protein Female Biomarkers |
| Zdroj: | Journal of Human Genetics. 61:473-481 |
| ISSN: | 1435-232X 1434-5161 |
| Popis: | Few mutations in cis have been annotated for F508del homozygous patients. Southern Italy patients who at a first analysis appeared homozygous for the F508del mutation (n=63) or compound heterozygous for the F508del and another mutation in the cystic fibrosis transmembrane conductance regulator gene (n=155) were searched for the A238V mutation in exon 6. The allelic frequency of the complex allele [A238V;F508del] was 0.04. When the whole data set was used (comprised also of 56 F508del/F508del and 34 F508del/other mutation controls), no differences reached the statistical significance in the clinical parameters, except chloride concentrations which were lower in [A238V;F508del]/other mutation compared with F508del/other mutation (P=0.03). The two study groups presented less complications than the control groups. Within the minimal data set (34 F508del/F508del, 27 F508del/other mutation, 4 [A238V;F508del]/F508del cases and 5 [A238V;F508del]/other mutation cases); that is, presenting all the variables in each patient, forced expiratory volume in 1 s and forced vital capacity presented a trend to lower levels in the study groups in comparison with the F508del/F508del group, and C-reactive protein approximated statistically significant higher levels in the [A238V;F508del]/other mutation as compared with F508del/F508del patients (P=0.09). The analysis of statistical dependence among the variables showed a significant anticorrelation between chloride and body mass index in the [A238V;F508del]/other mutation group. In conclusion, the complex allele [A238V;F508del] seems to be associated with less general complications than in the control groups, on the other hand possibly giving a worse pulmonary phenotype and higher systemic/local inflammatory response. These findings have implications for the correct recruitment and clinical response of F508del patients in the clinical trials testing the new etiological drugs for cystic fibrosis. |
| Databáze: | OpenAIRE |
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