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V Nunes

Publications and source records attributed to V Nunes.

At least 109 records · Page 6Linked to original sources
PubMed1992

Cystic fibrosis patients with mutation 1949del84 in exon 13 of the CFTR gene have a similar clinical severity as delta F508 homozygotes.

The majority of the identified cystic fibrosis (CF) mutations are very uncommon in the total patient population, making the correlation between the clinical presentation and the molecular alterations difficult. The largest deletion that has been described so far in CF is of 84 bp in exon 13, which corresponds to the regulatory (R) domain of the CF transmembrane conductance regulator (CFTR) protein. We have analysed 340 Spanish CF patients for this deletion, named 1949del84, and found three further compound heterozygous patients for mutations 1949del84 and delta F508, and one for 1949del84 and an unknown mutation. Evaluation of the clinical data in these patients suggests that this in-frame deletion, when associated with delta F508, has a similar disease severity to that of delta F508 homozygous patients.

Adolescent↗
PubMed1992

Incidence and expression of the N1303K mutation of the cystic fibrosis (CFTR) gene.

The N1303K mutation was identified in the second nucleotide binding fold of the cystic fibrosis (CF) gene last year. We have gathered data from laboratories throughout Europe and the United States of America in order to estimate its frequency and to attempt to characterise the clinical manifestations of this mutation. N1303K, identified on 216 of nearly 15,000 CF chromosomes tested, accounts for 1.5% of all CF chromosomes. The frequency of the N1303K allele varies significantly between countries and ethnic groups, being more common in Southern than in Northern Europe. This variation is independent of the delta F508 allele. It was not found on UK Asian, American Black or Australian chromosomes. N1303K is associated with four different linked marker haplotypes for the polymorphic markers XV-2c, KM.19 and pMP6d-9. Ten patients are homozygous for this mutation, whereas 106 of the remainder carry one of 12 known CF mutations in the other CF allele. We classify N1303K as a "severe" mutation with respect to the pancreas, but can find no correlation between this mutation, in either the homozygous or heterozygous state, and the severity of lung disease.

Base Sequence↗
PubMed1992

[Formation of left ventricular thrombus in acute myocardial infarction: significance of the determination of fibrinogen, of products of fibrinogen degradation, and of plasminogen].

OBJECTIVE: To evaluate the significance of the fibrinogen, the plasminogen and the fibrinogen degradation products levels as marks of left intraventricular thrombosis (LIVT) in acute myocardial infarction (AMI). METHODS: 219 consecutive patients of AMI admitted in a Coronary Care Unit of an University Hospital, were prospectively studied. All protocols included a clinical evaluation, an M-mode and 2D echocardiographic study and blood samples, at day 1, 3, 7 and at hospital discharge. In the intraventricular thrombus evaluation just the 4 Asinger grade was considered. In the laboratory evaluation we used: the Clauss chronometric method for the fibrinogen, the colorimetric method for the plasminogen and the agglutination in plaque for the FDP. The patients with ECO in the 2 or 3 Asinger grades and those in which ECO and laboratory study were not performed in the same day, were excluded. 101 patients remained on the study, and they were divided in two groups: 53 patients with LIVT and 48 patients without it. RESULTS: In both groups the fibrinogen raised along the first six days of the AMI, however in the group with LIVT this level didn't raise as high as in the group without LIVT (p < 0.001). In the FDP evaluation two peaks were found, one at 48 hours and another on the 6 th day, but there were no differences between the two groups. The plasminogen values raised along the first week of AMI, in a similar way in both groups. CONCLUSIONS: a) Fibrinogen levels raises in AMI, but this elevation is significantly smaller in the group with LIVT, which suggests fibrinogen consume in fibrin formation of the thrombus. b) FDP and plasminogen levels raise along the first week of AMI, but in a similar way in the two groups. c) None of these parameters permitted to individualize patients with thrombus formation.

Aged↗
PubMed1991

Analysis of 14 cystic fibrosis mutations in five south European populations.

We have analysed five Southern European populations (Albanian, Greek, Italian, Spanish and Yugoslavian) for 14 cystic fibrosis (CF) mutations. The most frequent mutations, apart from delta F508, were G542X (6.04%), R1162X (3.61%) and N1303K (3.24%). Each of the other analysed mutations were present at a frequency of less than 1% (R347P, R334W, S549RA, S549I, G551D, R553X and W1282X), and four mutations (D110H, delta I507, S549RT, and S1255X) were not found in this sample. The data presented here allows the use of mutation analysis in 69.5% of Spanish, 58% of Greek, and 56.5% of Italian CF cases.

Albania↗
PubMed1991

High conservation of sequences involved in cystic fibrosis mutations in five mammalian species.

Several mutations have been identified in the first nucleotide binding fold (NBF) of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene. We have analyzed the DNA sequences of exons 10 and 11 in five different mammalian species, marmoset, mouse, cow, pig, and sheep; the amino acid conservation studied for nine disease mutations; and two "benign" mutations. For exon 10, 87% homology at the DNA level and 93.5% at the amino acid level were found for these species. For exon 11, the lowest homology (70%) was found in mouse and the highest in marmoset (93%), whereas the amino acid sequence conservation ranged from 82.5 to 100%. All codons involved in CF mutations are highly conserved throughout evolution.

Amino Acid Sequence↗
PubMed1991

CA/GT microsatellite alleles within the cystic fibrosis transmembrane conductance regulator (CFTR) gene are not generated by unequal crossingover.

The gene responsible for cystic fibrosis (CF) has recently been identified, and a three-nucleotide deletion (delta F508 mutation) that results in the loss of a phenylalanine residue in the first putative ATP-binding domain of the predicted protein (CF transmembrane conductance regulator, CFTR) has been found to be the major CF mutation. Although several other mutations have been identified in the CFTR gene, most of them are very rare, making their application to genetic diagnosis difficult. While characterizing the genomic region encompassing the CF locus, we have identified three CA/GT blocks that flank exon 9 of the CF gene. One of the CA/GT blocks exhibits a highly informative variable number of dinucleotide repeats (VNDR) polymorphism. This intragenic VNDR microsatellite should, by itself, provide full information for genetic analysis in approximately 80% of CF families and will help elucidate the associations between DNA polymorphism haplotypes and specific gene mutations. Haplotype analyses of CF chromosomes with and without the delta F508 mutation suggest that the different alleles are generated by slipped-strand mispairing within the dinucleotide repeat during DNA replication, rather than by unequal crossingover within a recombination hot spot.

Alleles↗
PubMed1991

The search for south European cystic fibrosis mutations: identification of two new mutations, four variants, and intronic sequences.

The major mutation in the cystic fibrosis (CF) gene is a 3-bp deletion (delta F508) in exon 10. About 50% of the CF chromosomes in Southern Europe carry this mutation, while other previously described mutations account for less than 4%. To identify other common mutations in CF patients from the Mediterranean area, we have sequenced, exon by exon, 16 chromosomes that did not show the delta F508 deletion from a selected panel of eight unrelated CF patients. We describe here one missense and one nonsense mutation, and four sequence polymorphisms. We have also found two previously reported mutations in three chromosomes. Overall, these mutations may account for about 20% of CF alleles in the Italian and Spanish populations. No other mutations were detected in 10 out of 16 CF chromosomes after analyzing about 90% of the coding region of the CF gene, and 39 out of 54 intron/exon boundaries. Therefore, about 26% of CF mutations remain to be identified. In addition we provide the intron/exon boundary sequences for exons 4 to 9. These results together with previously reported linkage data suggest that in the Mediterranean populations further mutations may lie in the promoter region, or in intron sequences not yet analyzed.

Base Sequence↗
PubMed1991

Mutation and linkage disequilibrium analysis in genetic counselling of Spanish cystic fibrosis families.

We have analysed haplotypes for four DNA polymorphisms, closely linked to the cystic fibrosis (CF) gene, in 82 Spanish families, in which the CF probands are either homozygous for non-delta F508 mutations or heterozygous for the delta F508 deletion and other CF mutations. The analysis provides genetic data for a new polymorphism for the closely linked marker pKM.19, which is very strongly associated with CF. Haplotypes generated with the four marker loci are also in strong disequilibrium with the non-delta F508 CF chromosomes. The data reported here are useful in 1 in 4 risk pregnancies of parents who have no living affected child, and when counselling close relatives of CF families who are negative for the major CF mutation. The data presented are useful in our population, in which the majority of CF mutations, apart from the delta F508 deletion, are uncommon. For other populations in which mutation heterogeneity is also very high, it still might be more feasible to use RFLPs for diagnostic purposes, when analysis for common mutations is negative and DNA is available from the index patient. The experience presented here provides a model for these population groups who in turn should obtain their own haplotype data. In addition, the model system for genetic counselling presented here might also be useful for other genetic disorders.

Chromosome Deletion↗