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F Zolezzi

Publications and source records attributed to F Zolezzi.

16 recordsLinked to original sources
PubMed2000

Studies of the murine DDB1 and DDB2 genes.

Human DDB (Damaged DNA Binding protein) is a heterodimer of 48 and 127kDa subunits whose activity is absent from cell strains derived from a subset of Xeroderma Pigmentosum (XP) complementation group E individuals (Ddb(-)) [Keeney, S., Wein, H., and Linn, S., (1992). Mut. Res. 273, 49-56]. Whereas in vivo DNA repair appears to be compromised in both Ddb(-) and Ddb(+) XPE cells, DDB activity is not necessary for nucleotide excision repair (NER) in vitro. In this study, the presence of a specific UV-damaged DNA binding activity in mouse cell-free extracts that is comparable to the activity observed in HeLa cells was demonstrated. The mouse DDB2 cDNA, coding for DDB p48 subunit, was cloned and the partial genomic structure of DDB2 was obtained. A search of current databases revealed amino acid sequences of mouse and Drosophila predicted p127 homologues, but not of a Drosophila p48 homologue. The alignment of these higher eukaryotic p127 sequences uncovered the presence of three highly conserved domains in the p127 polypeptides which we hypothesize could function in DNA binding, transcription-transactivation, and protein-protein interaction, respectively.

Amino Acid Sequence↗
PubMed1998

Variable penetrance of familial pheochromocytoma associated with the von Hipple Lindau gene mutation, S68W. Mutations in brief no. 150. Online.

Van Hippel-Lindau disease (VHL) is an autosomal dominantly inherited disorder, characterised by the development of clear cell renal carcinomas, CNS hemangioblastomas, retinal angiomas, pancreatic tumors, pheochromocytomas and hepatic cysts. Recently a number of families with dominant familial pheochromocytoma as the only clinical manifestation have been reported to carry mutations in the HVL gene. We describe a family in which a novel VHL S68W mutation was segregating and carrier individuals manifested with variable penetrance of isolated pheochromocytomas. Investigation of this kindred confirmed that a mutation in the VHL gene could produce isolated pheochromocytomas as the only clinical feature and was variably penetrant.

Genes, Tumor Suppressor↗
PubMed1997

Mutation producing alternative splicing of exon 26 in the COL1A2 gene causes type IV osteogenesis imperfecta with intrafamilial clinical variability.

We have characterized a familial form of osteogenesis imperfecta (OI). Following the identification by ultrasound of short limbs and multiple fractures in a fetus at 25 weeks of gestation, the family was referred with a provisional diagnosis of severe OI. We detected subtle clinical and radiological signs of OI in the father and in the paternal grandmother of the proposita, who had never received a diagnosis of OI. Linkage analysis indicated COL1A2 as the disease locus. Heteroduplex analysis of reverse transcription-polymerase chain reaction (RT-PCR) amplification products of pro alpha2(I) mRNA from an affected member and subsequent sequencing of the candidate region demonstrated the presence of normal transcripts and a minority of transcripts lacking exon 26 (54 bp) of COL1A2. Sequencing of PCR-amplified genomic DNA identified an A --> G transition in the moderately conserved +3 position of the IVS 26 donor splice site. The mutant pre-mRNA molecules were alternatively spliced, yielding both full-length and deleted transcripts that represented less than 30% of the total pro alpha2(I) mRNA. The biochemical data on type I collagen synthesized by dermal fibroblasts showed intracellular retention of the mutant protein; failure to detect the shortened alpha2(I) chains either in the medium or in the cell layer may be the consequence of their instability at physiological temperature. These observations justified the mild resulting phenotype.

Adult↗
PubMed1996

Intrafamilial variable expressivity of osteogenesis imperfecta due to mosaicism for a lethal G382R substitution in the COL1A1 gene.

Fibroblasts from a 23 week old fetus affected with lethal (type II) osteogenesis imperfecta (OI) produced normal and abnormal type I procollagen molecules. The abnormal molecules were shown to contain pro alpha 1(I) chains in which the glycine at position 382 of the triple helical domain was substituted by arginine, as the result of a G-to-C transversion at nucleotide 1797 of the pro alpha (I) coding sequence. Also fibroblasts from the apparently normal father produced abnormal type I collagen but the overmodified alpha 1(I) chains tended to disappear with increasing passage number. We determined that the mutant allele accounted for approximately 36% of the COL1A1 alleles in the father's skin fibroblasts. Upon careful clinical reexamination, the man appeared to be very mildly affected with OI. The most plausible explanation for such a phenotypic variation is that the father is a mosaic for a mutation that is lethal in the heterozygous son. This finding confirms previous observations that somatic mosaicism for new dominant mutations is responsible for extreme intrafamilial variability and poses some caveats in genetic counselling.

Arginine↗
PubMed1994

Severe (type III) osteogenesis imperfecta due to glycine substitutions in the central domain of the collagen triple helix.

The molecular defects responsible for three cases of severe (type III) osteogenesis imperfecta (OI) were investigated. The mutation sites were localized in pro alpha 1(I) and pro alpha 2(I) mRNA molecules, respectively, by chemical cleavage of mismatch in heteroduplex nucleic acids. Mutation identification was achieved by reverse transcription-polymerase chain reaction-DNA amplification, followed by cloning and sequencing. Two unrelated patients were demonstrated to bear the same G-A transition at nucleotide 2418 of the pro alpha 1(I) coding region, leading to G589S substitution and resulting in very similar clinical manifestations. In the latter patient, a G-T transversion at nucleotide 2166 was found in one pro alpha 2(I) allele, which caused a G586V substitution and again severe OI. Presumably all three mutations occurred de novo in the probands, since they were not found in their parents' DNA. The biochemical findings on type I collagen were very similar in all the probands: the mutations here described had little destabilizing effects on triple helix formation, secretion and stability. The half-life of the collagen incorporated into the insoluble matrix was comparable with that of controls. These mutations are localized in the gap zone of the fibrils where mineral nucleation occurs. This fact suggests that they probably do not exert destabilizing effects on the individual collagen molecules, but rather on the mineralization process, once the defective molecules are incorporated into the fibrils, hence causing severe phenotypes.

Base Sequence↗
PubMed1993

Gly85 to Val substitution in pro alpha 1(I) chain causes mild osteogenesis imperfecta and introduces a susceptibility to protease digestion.

In this paper we describe a mild moderate form of osteogenesis imperfecta caused by a point mutation in COL1A1 which converted glycine 85 to valine. The valine substitution introduced into the triple-helical domain of type-I collagen a conformational perturbation causing susceptibility to digestive proteases. In fact, SDS/PAGE of pepsin-treated collagen showed the presence of a faint band, migrating between alpha 1(I) and alpha 2(I), both in the medium and in the cell layer. On trypsin digestion the band, a shortened form of alpha 1(I), had a melting temperature of 39.5 degrees C. If the triple-helical collagen was obtained after trypsin or chymotrypsin digestion of procollagen, two shortened bands were identified; the enzymes cleaved about 40% of the trimers. The mutant procollagen was normally secreted and processed in the extracellular matrix at a normal rate. When native type-I collagen was formed after dextran-sulfate incubation, only chains of normal length were found, suggesting that the fibroblast proteases did not recognize the alteration introduced by the mutation. The effects of glycine 85 to valine substitution are compared with those produced by a previously described arginine substitution of the same residue (Deak et al., 1991).

Adult↗
PubMed1986

Chronic myocarditis leading to a right ventricular cardiomyopathy. Case report.

A case of dilated cardiomyopathy arose after a spontaneous abortion at the second month of pregnancy is reported. Whereas clinical, hemodynamic and gross features pointed to a diagnosis of right ventricular cardiomyopathy, histologic findings of inflammatory infiltration, myocyte degeneration and interstitial fibrosis of the atrial and ventricular walls allowed to a correct diagnosis of chronic myocarditis.

Abortion, Spontaneous↗
PubMed1986

[Right cardiac echinococcosis with coronary compression. Description of a clinical case].

An outstanding case of cardiac echinococcosis is described. Clinical symptomatology was characterized by typical nitroglycerin-responsive crisis of angina pectoris associated to an electrocardiographic pattern of negative T wave on anterolateral and inferior leads. The diagnosis was suspected on the basis of thoracic computerized tomography and coronary arteriography. The anatomical localization was mainly pericardial but the right ventricle was involved too. Left anterior descending artery was dislocated and squeezed.

Adult↗
PubMed1983

[The association between liver cirrhosis and bacterial endocarditis. Description of a typical case].

A typical case of an association of cirrhosis of the liver and bacterial endocarditis involving only the aortic valve is described. The essential role of echocardiography in diagnosis and the ability of the technique to supply useful information for correct therapy is emphasised. Finally, evidence that, in spite of all negative blood cultures, Escherichia Coli via the urinary ways may be considered the aetiological agent is presented.

Aortic Valve↗
PubMed1983

[Complete sub-His AV block caused by carotid sinus massage. Possible direct vagal effect on the His-Purkinje system].

A 64 year old male patient, with frequent syncopes, underwent an electro-physiologic study. A complete left bundle branch block and a first degree His-Purkinje system atrioventricular block (AH = 100 msec, HV = 60 msec) were present in basal condition. Left carotid sinus massage caused extreme sinus bradycardia (with PP intervals as long as 3000 msec), without AH and HV interval changes. Right carotid sinus massage caused a His-Purkinje atrioventricular block. Ventricular asystole of 4800 msec occurred while the sinus cycle varied between 1440 and 590 msec. Since His-Purkinje atrioventricular block is induced by the right carotid sinus massage with PP intervals even shorter than the basal cycles and since the block was not reproduced at PP intervals longer than 1440 msecs, a direct vagal effect on the His-Purkinje system may be suggested, rather than a bradycardia dependent phase 4 block.

Bradycardia↗
PubMedDate not supplied

Allelic frequencies of FBN1 gene polymorphisms and genetic analysis of italian families with Marfan syndrome.

The fibrillin gene (FBN1) is the disease locus for Marfan syndrome. This disorder shows a high degree of clinical and allelic heterogeneity. Direct mutation screening has proven difficult and inefficient and at present cannot be utilized for routine analysis. In familial cases linkage analysis represents a useful tool for molecular diagnosis. We have determined the allelic frequencies of 5 polymorphic markers within the FBN1 locus in the Italian population and have successfully employed them for prenatal diagnosis and resolution of clinically equivocal cases.

Alleles↗