Search PubMed⌕ Search

Biomedical subjects

R Taramelli

Publications and source records attributed to R Taramelli.

52 records · Page 3Linked to original sources
PubMed1990

Lecithin cholesterol acyl transferase deficiency: molecular analysis of a mutated allele.

The enzyme, lecithin cholesterol acyltransferase (LCAT), is responsible for the esterification of plasma cholesterol mediating the transfer of an acyl group from lecithin to the 3-hydroxy group of cholesterol. Deficiency of the enzyme is a well-known syndrome with a widespread geographic occurrence. We have cloned an allele from a patient homozygous for the LCAT deficiency. The only change that we could detect is a C to T transition in the fourth exon of the gene; this causes a substitution of Arg for Trp at position 147 of the mature protein. The functional significance of such a substitution with respect to the enzyme defect was demonstrated by transfecting the mutated LCAT gene in the cell line COS-1.

Alleles↗
PubMed1990

A new constitutively activating mutation of the Gs protein alpha subunit-gsp oncogene is found in human pituitary tumours.

A new 227 Gln----Lys oncogenic mutation of the Gs alpha subunit (the GTP-binding protein that stimulates adenylyl cyclase) has been found in three out of eight human growth hormone-secreting pituitary tumours of the group 2, characterized by high cAMP and constitutively activated adenylyl cyclase. The additional five group 2 tumours expressed another, previously described mutation, 201 Arg----Cys, while the tumours of group 1, characterized by normal cAMP and adenylyl cyclase activity, expressed neither these nor the two other mutations of the same sites previously described in group 2. The Gln 227 site of alpha s corresponds to the Gln 61 site in the low Mw G protein, p21 ras, where the Leu substitution had already been shown to be oncogenic. The oncogenic potential (gsp oncogene) of the mutations so far observed depends on the reduced GTPase activity intrinsic to alpha s, with constitutive activation of the protein and marked elevation of cAMP. The latter is the intracellular messenger that stimulates growth of pituitary growth hormone-secreting cells and other cell types.

Adenylyl Cyclases↗
PubMed1989

The homozygous state of G to A--117A gamma hereditary persistence of fetal hemoglobin.

During a study of Sardinian families with hereditary persistence of fetal hemoglobin (HPFH), two unrelated subjects with unusually elevated Hb F levels were identified. By selective amplification of the A gamma gene promoter and hybridization to synthetic oligonucleotides, we demonstrate that these subjects are homozygous for the -117A gamma G----A substitution that is responsible for a form of nondeletional HPFH. The hemoglobin synthetic pattern of these patients is discussed.

Adult↗
PubMed1988

Sardinian G gamma-HPFH: a T----C substitution in a conserved "octamer" sequence in the G gamma-globin promoter.

A survey of hemoglobinopathies in Northern Sardinia allowed the identification of two subjects heterozygous for a new type of G gamma hereditary persistence of fetal hemoglobin (HPFH). The G gamma-globin gene from the HPFH chromosome shows the presence of a T----C substitution 175 nucleotides upstream of the CAP site, adding a new example of single-point mutations occurring in the promoter region of the gamma-globin genes and linked to HPFH phenotypes. In this case the mutation affects the 3' end nucleotide of a conserved octamer sequence known to be present in other regulatory elements of several genes.

Base Sequence↗
PubMed1986

Gamma delta beta-thalassaemias 1 and 2 are the result of a 100 kbp deletion in the human beta-globin cluster.

The DNA spanning two large deletions in the human beta-globin gene cluster (gamma beta-thalassaemia 1 and 2) has been cloned by cosmid cloning and chromosomal walking. The entire region was mapped and analyzed for the presence of repetitive sequences. The results show that the affected loci have lost almost 100 kb of DNA in a deletion event not involving homologous or repetitive sequences.

Chromosome Deletion↗
PubMed1983

Delta thalassemia: a non-deletion defect.

Hematological and gene mapping studies of two Southern Italian children doubly heterozygous for delta 0-thalassemia and delta 0 beta 0-thalassemia have been carried out. No HbA2 was detectable by electrophoresis of total hemoglobin in these patients. Restriction enzyme analysis of the globin gene cluster with delta, gamma, epsilon and RIH cloned probes showed all the expected normal bands, in addition to the abnormal fragments related to a previously described type of delta 0 beta 0-thalassemic deletion, demonstrating an apparently intact globin gene cluster on the thalassemic chromosome. The relevance of this finding to models for coordinated expression of non alpha globin genes is discussed.

Adult↗
PubMed1983

A gene controlling fetal hemoglobin expression in adults is not linked to the non-alpha globin cluster.

The possible linkage between a gene causing heterocellular hereditary persistence of fetal hemoglobin (HPFH) and human non-alpha globin loci has been studied in a large Sardinian family. In this family a homozygous beta o-thalassemic patient was found, with an unusually mild form of this disease, which was ascribed to the co-existence of a gene causing heterocellular HPFH. DNA polymorphisms in the non-alpha globin cluster were analyzed by restriction enzyme digestion with HincII, HindIII and BamHI and with epsilon-, gamma-and beta-globin probes; the pattern of inheritance of these polymorphisms indicates that the HPFH gene is transmitted with one beta o-thalassemic gene in a single instance, with the second beta o-thalassemic gene in three instances and with a normal beta-globin gene in two cases. These data indicate that this HPFH gene is not linked to the non-alpha globin gene cluster, in contrast to previous observations with different HPFH genes, and suggest that this gene might code for diffusible substances acting, directly or indirectly, on gamma-globin gene expression.

Adult↗
PubMed1982

Molecular comparison of delta beta-thalassemia and hereditary persistence of fetal hemoglobin DNAs: evidence of a regulatory area?

The hematological phenotypes of several Mediterranean patients with delta beta-thalassemia and hereditary persistence of fetal hemoglobin have been characterized. Although clinical and hematological characteristics are essentially superimposable in all heterozygous delta beta-thalassemics, these patients show typical G gamma/A gamma ratios in their Hb F, ranging from approximately 0.07 in Sardinian to approximately 0.15 in Sicilian and approximately 0.35 in Spanish patients. A gamma Sardinian-(isoleucine-75 leads to threonine) is found in Spanish patients and accounts for all of the A gamma production in heterozygotes, indicating that persistent production of gamma chains occurs cis to the delta beta-thalassemia gene. The molecular heterogeneity of these conditions is demonstrated by restriction enzyme mapping of DNA; Sicilian and Calabrian patients show a deletion starting from the delta-globin intron and extending several kilobases 3' to the beta-globin gene; in Spanish patients the deletion starts approximately 2-3 kilobases 5' to the delta-globin gene and extends well beyond the beta-globin gene. Comparison of these deletions with previously described ones in Negro and in a new Southern Italian case of hereditary persistence of fetal hemoglobin suggests that the deletion of a region centered at a cluster of repetitive sequences approximately 3.5 kilobases 5' to the delta-globin gene may be critical for the persistent expression of high levels of gamma-globin in hereditary persistence of fetal hemoglobin compared to delta beta-thalassemia. The concept that the deletion or mutation of specific areas (rather than nonspecific changes brought about by large deletions in the globin cluster) is important in determining the persistent expression of gamma-globin genes is supported by the finding of a nondeletion type of delta beta-thalassemia in Sardinians.

Chromosome Deletion↗
PubMed1980

Organization of alpha-globin genes in Hb Hasharon (alpha 47 asp replaced by his) carriers.

Restriction enzymes analysis of the DNA from two unrelated Italian families with Hb Hasharon, a variant Hb (alpha 47asp replaced by his) frequently occurring in the Polesine area in Italy, indicates that this variant is associated to an alpha globin gene deletion. The alpha Hash genotype most likely results from a mutation on an alpha thal2 genotype.

Asparagine↗
PubMed1979

beta-Like globin RNA sequences in hemoglobin Lepore disease.

A Southern Italian patient homozygous for hemoglobin Lepore disease synthesizes approximately 3% Lepore delta beta-globin chains (relative to alpha chains) in the reticulocytes. Measurement of beta-like RNA sequences by hybridization to complementary DNA specific for beta-globin demonstrates a low level (1--2% relative to alpha sequences) of these sequences in cytoplasmic RNA from reticulocytes or spleen cells, suggesting that the Lepore gene is expressed into mRNA at a lower extent than normal alpha or beta genes; the comparison with the level of beta-like sequences found in nuclear RNA (6--8%) further supports this conclusion and indicates, in addition, that Lepore RNA might be degraded at a faster rate than normal. 2--3% beta-like sequences are found in nuclear RNA in three cases of homozygous beta0-thalassemia, setting the highest possible estimate for the delta-RNA level; this figure suggests that the 'delta-promoter'-dependent Lepore delta beta gene is somehow more actively expressed than the delta gene.

Globins↗