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J Lavinha

Publications and source records attributed to J Lavinha.

47 records · Page 3Linked to original sources
PubMed1992

[Diagnosis of Lepore hemoglobinopathy with DNA analysis].

We illustrate the application of recombinant DNA methods (namely Southern blotting) for the genotype diagnosis of haemoglobin Lepore Boston: the use of the restriction endonucleases PstI and XbaI along with a beta globin gene specific probe make it possible to detect a deletion of approximately 7kb which typically characterizes the delta beta Boston gene. The impact of using such methods in the prenatal diagnosis of major haemoglobinopathies is discussed.

Adult↗
PubMed1991

Alpha-thalassemia resulting from deletion of regulatory sequences far upstream of the alpha-globin structural genes.

We describe an alpha-thalassemia determinant in which alpha-globin expression is silenced by a deletion located 27 kb 5' to the transcription start site of the alpha 2-globin gene. This alpha-thalassemic determinant, (alpha alpha)MM, is a member of a newly described group of thalassemic mutations resulting from deletion of locus-controlling sequences critical to globin gene expression.

Amino Acid Sequence↗
PubMed1991

A fertile male with cystic fibrosis: molecular genetic analysis.

A family study is presented in which the father of a girl with severe cystic fibrosis (CF) was also found to have CF but was mildly affected. He was diagnosed with three positive sweat tests including one after suppression with fludrocortisone. Genetic analysis showed that he is a compound heterozygote with the delta F508 CF mutation associated with haplotype B and a second CF mutation associated with haplotype C. In this unusual, fertile CF male, the late age of diagnosis (30 years) and the mild clinical picture suggest that the compound genotype (delta F508/other CF mutation) determines a much less severe form of the disease which might have gone unnoticed in the absence of a severely affected child. The implications of these findings for genetic counselling of families with CF are discussed.

Adult↗
PubMed1990

Cystic fibrosis in the Portuguese population: haplotype distribution and molecular pathology.

The aim of this study was to obtain an estimate of the frequency of the delta F508 mutation in the Portuguese population, and of the tightness of its association with specific haplotypes. Furthermore, the genotype/clinical phenotype relationship and the feasibility of prenatal diagnosis were also investigated. The analysis of 42 cystic fibrosis (CF) families revealed that (1) 52% of CF chromosomes carry the deletion of codon 508; (2) there seems to be a positive correlation between the occurrence of the delta F508 mutation and the severity of the disease; and (3) fully informative prenatal diagnosis can be offered in 76% of at-risk pregnancies by using both genomic and allele specific oligonucleotide probes.

Chromosome Deletion↗
PubMed1990

Unusual molecular basis of Hb H disease in the Azores Islands, Portugal.

An Azorean family with Hb H disease (10% Hb H) was studied in order to elucidate its molecular basis. DNA studies on the patient only revealed a 4.2 kb "leftward" deletion of paternal origin which implies the co-inheritance of a nondeletional alpha-thalassemia determinant. Restriction endonuclease and oligonucleotide analysis allowed the exclusion of five point mutations: initiation codon (at both alpha 1- and alpha 2-globin genes), IVS-I donor splice junction pentanucleotide deletion, codon 125 CTG----CCG substitution, and Saudi Arabian polyadenylation signal mutation. These findings suggest that the molecular basis of this form of Hb H disease is probably different from those described previously.

Azores↗
PubMedDate not supplied

Heterogeneous ethnic distribution of the 844ins68 in the cystathionine beta-synthase gene.

A novel mutation in the cystathionine beta-synthase (CBS) gene (a 68-bp insertion in the coding region of exon 8: 844ins68) was recently described, but its prevalence in different human populations is unknown. We analyzed the prevalence of the 68-bp insertion in the CBS gene in 405 unrelated individuals (810 chromosomes) of European, African, Asian and Amerindian origins. PCR amplification of a DNA fragment containing exon 8 of the CBS gene was employed. In addition, screening for the T833C CBS mutation by BsrI digestion was carried out in all samples bearing the 844ins68 mutation, since both mutations were previously reported to be associated in cis. The insertion was found in heterozygosity in 14 out of 104 whites (13.5%), was absent among Asians, and was found solely in 1 out of 220 Amerindian chromosomes analyzed, whereas a much higher prevalence was observed among blacks (37.7% of heterozygotes and 4% of mutant homozygotes). Furthermore, the T833C CBS mutation was found to cosegregate in cis with 844ins68 in all carriers of the insertion. The finding of the double mutant among blacks and Caucasians suggests that it antedated the racial divergence between Africans and non-Africans, and provides evidence for a partly or completely neutralizing effect conferred by the 68-bp insertion, since it allows the skipping of the T833C mutation. Our study represents the first analysis of the 844ins68 insertion in the CBS gene in different human populations, and reveals an extensive ethnic and geographic variability associated with this mutation.

Cystathionine beta-Synthase↗
PubMedDate not supplied

[The molecular basis of dominantly inherited beta-thalassemia].

In this study, we sought to clarity the molecular basis of a dominant inherited beta-thalassemia, found in heterozygosity in a northern Portuguese family with thalassemia intermedia. We characterized: i) the alpha-globin gene cluster structure; ii) the beta-globin gene cluster haplotype; and iii) the beta-thalassemia mutation. The alpha-globin gene cluster was structurally normal. The G-->T transversion at codon 121 of the beta-globin gene was found in the affected individuals in association with Orkin's haplotype V. This is an uncommon, though ubiquitous, mutation. Which has also been found, in association with different haplotypes, in several distant populations. It has only been observed in this three-generation family, in the Portuguese population. We suggest a mechanism to explain the genotype/phenotype correlation.

Adult↗
PubMedDate not supplied

DNA polymorphisms associated with the factor VIII:C gene in the Portuguese population.

We have determined the allele frequencies of seven restriction fragment length polymorphisms within or close to factor VIII:C gene in the Portuguese population. The allele frequency of all studied intra- and extragenic biallelic polymorphisms does not differ significantly from those found in other European or Asian populations. On the contrary, the distribution of the different alleles of the TaqI RFLP at the DXS52 locus revealed similarity only with Algerians. We observed a correspondence between the TaqI and BclI alleles at this locus.

Algeria↗
PubMedDate not supplied

[Neonatal screening of hemoglobinopathies in a population residing in Portugal].

The primary objective of newborn screening of hemoglobinopathies is the early identification of infants with sickle cell disease, as they are at increased clinical risk. Other goals include the identification of other types of clinically significant hemoglobinopathies and the detection of heterozygous carriers followed by the screening and counselling of family members. We performed a pilot study for the neonatal screening of hemoglobinopathies in 400 samples of cord blood taken from a maternity in Lisbon. We did not find any newborn with sickle cell disease. Six samples were from sickle cell heterozygotes, the respective families were studied and informed. We looked for the presence of alpha-thalassemia at birth in 100 consecutive samples of cord blood, by the presence of Hb Bart's, abnormal red blood cell indices and alpha-globin genotype. The results show an incidence of 10% of alpha-thalassemia (-alpha) carriers and 4% of triple alpha-globin gene carriers. The authors discuss the feasibility of neonatal screening of hemoglobinopathies in a Portuguese-speaking population consisting of a low prevalence of Hb S trait autoclonous group and a high prevalence immigrant minority.

Carrier State↗
PubMedDate not supplied

[Mucoviscidosis with respiratory symptomatology in the neonatal period].

A case of cystic fibrosis presented in the neonatal period with respiratory symptomatology associated with early pancreatic insufficiency is reported. The CFTR gene molecular analysis was found to be a compound heterozygotes for delta F508 and G542X. The rarity of this mode of presentation and the inclusion of this entity in the differential diagnosis for neonatal respiratory distress syndrome is emphasised. The pathogenesis and some therapeutic aspects carried out in our patient, which might have improved the life expectancy of patients with this disease, are discussed.

Cystic Fibrosis↗