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Biomedical subjects

C Camaschella

Publications and source records attributed to C Camaschella.

At least 55 records · Page 3Linked to original sources
PubMed1996

Analysis of microsatellite instability in chronic lymphoproliferative disorders.

Microsatellite instability (MSI) represents one specific pattern of genomic instability and is one of the genetic lesions most frequently detected in human neoplasia. Although MSI has been found to be associated with a wide variety of solid cancers, its involvement in lymphoid malignancies is virtually unexplored. In this study, we have investigated the presence of MSI in chronic lymphoproliferative disorders by comparing the pattern of nine microsatellite repeats (two tetranucleotides, two trinucleotides, and five dinucleotides) on autologous germline and tumor DNA of 23 patients, including 17 with B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (B-CLL/SLL), four with hairy cell leukemia, one with lymphoplasmacytoid lymphoma, and one with T-cell chronic lymphocytic leukemia. All samples at diagnosis displayed a germline pattern of the microsatellites examined, thus suggesting that MSI is not involved in the pathogenesis of these lymphoproliferations. Also, no microsatellite alterations were observed in consecutive samples of B-CLL/SLL obtained from the same patient at various stages of the disease both before and after chemotherapy. Conversely, alterations in 3/9 microsatellite repeats were detected in one case of Richter's syndrome which had evolved from a pre-existent B-CLL/SLL phase. Overall, the low frequency of MSI among chronic lymphoproliferative disorders adds further weight to the common view that the mechanisms and patterns of genomic instability in lymphoid neoplasia differ markedly from those commonly observed in solid cancers.

Base Sequence↗
PubMed1996

Allelic association of microsatellites of 6p in Italian hemochromatosis patients.

Hemochromatosis (HC) is an inherited disorder of iron metabolism and is frequently seen in Caucasians. The biochemical defect and the responsible gene are unknown, but the HC locus is closely linked to HLA-A on human chromosome 6 in the region 6p21.3. Although extensive studies have been performed in several populations, the precise location of the gene is still undefined. Linkage disequilibrium with HC has been detected for loci that are 3 cM apart: HLA class I and D6S105, which is located on the telomeric side of HLA-A. We have analyzed the inheritance of several multi-allele polymorphisms that map to 6p (D6S265, Y52, HLA-F, D6S306, D6S105, D6S464, D6S299) in 34 Italian HC families and in 17 unrelated patients. Significant association with HC was shown for alleles of multiple markers in the HLA-A region, for the distant marker D6S105, but not for the D6S299 marker at 4 cM from HLA-A on the telomeric side. HC status was unambiguously assigned to 70 affected and 63 unaffected chromosomes from family studies. Thirty five different haplotypes were found in 70 HC chromosomes when considering four markers most tightly associated with the disease. A predominant haplotype comprising alleles 1-3-1-8 (marker order D6S265, HLA-A, Y52, D6S105) accounted for 30% of the HC chromosomes and was absent in normals. A minority of other HC haplotypes could be related to the major haplotype by assuming single crossover events. Results of haplotype studies suggest a founder effect in the Italian population, as previously shown in Australian patients, and a possible common mutation shared with affected individuals of Celtic origin.

Alleles↗
PubMed1996

The ancestral hemochromatosis haplotype is associated with a severe phenotype expression in Italian patients.

We evaluate the relation between genotype and phenotype in 47 Italian male patients with homozygous genetic hemochromatosis (GH). Phenotype evaluation was based on the ratio of amount of iron removed (IR) by phlebotomy and age (IR/age). Patients were divided in two classes of phenotype expression: class I included 26 patients with less severe iron overload (IR/age <0.33) and class II included 21 patients with a more marked one (IR/age >0.33). Genetic variability was assessed by haplotype analysis combining alleles at HLA-B, D6S265, HLA-A, and D6S105 loci. A common ancestral haplotype carrying D6S265-1, HLA-A3, and D6S105-8 alleles was present in 13 of 52 (25%) chromosomes in class I and in 24 of 42 (57%) chromosomes in class II (P = .0027). Homozygotes and heterozygotes for the ancestral haplotype had higher iron indices than patients carrying two haplotypes other than the ancestral one. Seven of the eight patients homozygous for the ancestral haplotype were in class II, heterozygotes were equally distributed between the two classes, whereas 14 of 18 carriers of other haplotype combinations were in class I. Our results suggests that the gene defect linked to the ancestral haplotype is the result of a single, severe mutation. The high variability of phenotype expression in heterozygotes for the ancestral haplotype could be accounted for the contribution of the mutation carried by the second haplotype. Combination of different mutations could be responsible for the variable degrees of iron overload found in patients with GH.

Adult↗
PubMed1995

Characterization of mitochondrial DNA in primary cardiomyopathies.

With the aim of studying the involvement of the mitochondrial genome in the impairment of heart function, mitochondrial DNA was analyzed by modified primer shift-polymerase chain reaction in a panel of young patients affected by primary cardiomyopathies. Mitochondrial DNA molecules harboring the 7436 bp deletion were specifically found in cardiomyopathic patients as compared with a panel of control subjects. The 4977 bp deletion was commonly detected among the subjects analyzed whereas none of the specific tRNA gene point mutations generally associated with the cardiomyopathic trait were detected. The presence of the 7436 bp deletion as a consequence of a premature aging of the heart muscle, secondary to heart dysfunction, is discussed.

Adult↗
PubMed1995

Genetic interactions in thalassemia intermedia: analysis of beta-mutations, alpha-genotype, gamma-promoters, and beta-LCR hypersensitive sites 2 and 4 in Italian patients.

In order to verify the genetic factors influencing the clinical expression of beta-thalassemia we have studied 292 Italian patients, 165 with thalassemia intermedia and 127 with thalassemia major. The beta-globin gene mutations were defined in all cases. The number of alpha-globin genes and the integrity of specific control regions of the beta-globin cluster--gamma promoters and beta-Locus Control Region (beta-LCR)--were studied in selected cases. Homozygosity for mild mutations (group I) accounts for 24% of the intermedia patients and it is not represented among major patients. Forty-four percent of intermedia patients had combinations of mild/severe (group II) mutations and 32% had homozygosity or double heterozygosity for severe mutations (group III). Seventy-six percent of patients with thalassemia major were classified in group III and 24% in group II. Deletion type-alpha3.7 thalassemia, assessed in a part of the cases, was found in 5% of thalassemia major and 19.5% of intermedia patients in groups II and III. Structural analysis of gamma promoters and beta-LCR HS2 and HS4 regions, carried out in order to look for alterations associated with Hb F increase, did not reveal new mutations. Only rare polymorphic changes were observed at the HS2 and HS4 level. The -158G gamma C T change was found with an increased incidence in intermedia patients in groups II and III. A subset of 10 beta-thalassemia heterozygotes with mild intermedia phenotype resulted from coinheritance of a triplicated alpha-locus. We have been unable to find a molecular basis for the benign clinical course in approximately 20% of patients with thalassemia intermedia. Other genetic or acquired factors must be hypothesized which ameliorate the clinical condition.

Adolescent↗
PubMed1995

New polymorphisms and markers in the HLA class I region: relevance to hereditary hemochromatosis (HFE).

Hereditary hemochromatosis (HFE) is an inherited disorder whose gene lies in the proximity of the histocompatibility antigen (HLA) class I region, on 6p21.3. Despite efforts in refining the HFE region, a number of informative DNA markers, linked to the disease locus and amenable to use in an assay based on the polymerase chain reaction (PCR) is available. The gene content of this region is high, and the HFE gene has not so far been identified. We have used a strategy based on PCR protocols potentially able to detect both polymorphisms and expressed sequences. This approach has been applied to a 700-kb stretch (approximately) of DNA corresponding to the insert of a Centre d'Etude du Polymorphisme Humain yeast artificial chromosome (225 B1) of the possible candidate region. Five new polymorphisms have been detected among 20 specific fragments isolated. Four of them are tightly linked to the HFE locus. Because of the strong linkage disequilibrium with the disease demonstrated by these markers, they could represent starting points for the identification and characterization of the HFE gene. The remaining non-polymorphic fragments, being amplifiable and in most cases linked to NotI sites, may be useful starting points for the generation of a genomic contig of band 6p21.3 and for gene identification.

Base Sequence↗
PubMed1995

[Hypertrophic obstructive cardiomyopathy in a patient with Turner syndrome].

A case of hypertrophic obstructive cardiomyopathy in a patient with Turner syndrome is reported. The most frequently associated cardiac anomalies are coarctation of the aorta and bicuspid aortic valve. Hypertrophic cardiomyopathy has never been reported in this syndrome but is frequent in Noonan syndrome. In these two conditions the phenotype may be indistinguishable but the cariotype is different: normal in Noonan and 45X in Turner syndrome. Our patient had the typical somatic features, and the cariotype was 45X in all examined cells. A familial form of hypertrophic cardiomyopathy was excluded by the normal clinical examination of other members of the family. The presence of hypertrophic cardiomyopathy also in Turner syndrome and the recent localization on the long arm of the chromosome 12 of the gene for Noonan syndrome might postulate a common pathogenesis of the two syndromes.

Cardiomyopathy, Hypertrophic↗
PubMed1994

Interaction of rare illegitimate recombination event and a poly A addition site mutation resulting in a severe form of alpha thalassemia.

The clinical diversity of thalassemia depends on interaction of diverse genetic defects. We have characterized a severe form of alpha thalassemia caused by coinheritance of a rare alpha-globin gene deletion and a nondeletional defect in a southern Italian family. The proband, a 7-year-old girl, exhibited an abnormal hemoglobin electrophoresis pattern with hemoglobin H and hemoglobin Barts, indicating inheritance of H and hemoglobin Barts, indicating inheritance of a severe form of alpha thalassemia. Southern blot analysis of DNA showed normal as well as aberrant alpha-globin gene fragments indicating heterozygosity for a deletional form of alpha thalassemia in the proband and her mother. The coinheritance of a nondeletional form of alpha thalassemia (alpha alpha T) was suspected because of the severity of the proband's phenotype and the presence of normal alpha-globin gene fragments in the father. Selective polymerase chain reaction of the paternal alpha 1- and alpha 2-globin genes in the proband followed by DNA sequence analysis showed an AATAAA to AATGAA mutation in the polyadenylation signal sequence of the alpha 2-globin gene. Genomic DNA mapping and sequence analysis of a unique polymerase chain reaction product generated across the deletion breakpoint of the maternal allele showed a 5,201-bp deletion extending from 870 nucleotides 5' of the alpha 2-globin gene to nucleotide +519 in the alpha 1-globin gene. This deletion is similar to that previously suggested by blotting studies in a Greek family (Pressley et al, Nucleic Acids Res 8:4889, 1980) and removes the entire alpha 2-globin gene and a portion of the 5' end of the alpha 1-globin gene. Sequence characterization of the resultant aberrant truncated alpha 1-globin gene from the proband showed a 27 nucleotide duplication corresponding to the 3' end of the alpha-globin gene IVS-2 region separated by the insertion of a tetranucleotide (GGTT), suggesting that this deletion is caused by an illegitimate recombination event.

Base Sequence↗
PubMed1994

Human peripheral blood granulocytes and myeloid leukemic cell lines express both transcripts encoding for stem cell factor.

Stem cell factor (SCF), the ligand for the c-kit proto-oncogene, has been shown to play a critical role in the migration of melanocytes and germ cells during embryogenesis as well as in the proliferative control of the hematopoietic compartment. In this study we investigated the expression of both the soluble and transmembrane SCF forms in purified peripheral blood populations and in several hematopoietic cell lines. Expression of both transcripts, though in different ratios, was identified in whole bone marrow, in bone marrow stromal cells and in human peripheral blood. In peripheral blood, SCF expression could be ascribable to polymorphonuclear leukocytes (PMN), whereas no SCF expression was detected in isolated lymphocytes, monocytes and in some T lymphoid cell lines. Conversely, some hematopoietic myeloid cell lines, such as HL-60, KG1 and K562, express SCF with similar patterns.

Base Sequence↗
PubMed1994

A unique origin for Sicilian (delta beta) (0)-thalassemia in 33 unrelated families and its rapid diagnostic characterization by PCR analysis.

Direct sequencing and restriction enzyme digestion of the polymerase chain reaction (PCR) product encompassing the breakpoint were used to characterize the Sicilian (delta beta)(0)-thalassemia deletion in 33 unrelated Italian subjects. All cases showed the same sequencing features at the breakpoint region, suggesting a unique origin for this deletion in Italy. We also describe a one-step PCR assay for the rapid screening of homozygotes and carriers of Sicilian (delta beta) (0)-thalassemia by the simultaneous use of three specific oligonucleotides. This procedure could have an impact on genetic counseling of couples at risk for this type of thalassemia, and with respect to compound heterozygotes bearing a Sicilian chromosome.

Base Sequence↗
PubMed1994

A new complex polymorphic repeat close to the HLA-A and HLA-E loci.

We describe a complex polymorphic repeat discovered analyzing YAC 225B1, which spans the region between the HLA-A and HLA-E loci. The repeat consists of a variable number of the nucleotide A followed by a variable number of the trinucleotide AAG [(A)n(AAG)n]. Three different alleles were detected with an observed heterozygosity of 0.30.

Alleles↗
PubMed1994

Clinical and haematological improvement induced by etidronate in a patient with idiopathic myelofibrosis and osteosclerosis.

We report a patient with agnogenic myeloid metaplasia associated with debilitating bone pain due to increased bone turnover and osteosclerosis. Treatment with etidronate at a dose of 6 mg/kg per day on alternate months resulted in a complete recovery of bone symptoms and normalization of metabolic parameters of bone turnover; unexpectedly, a sustained haematological improvement was also observed after several months of therapy, suggesting that bone marrow microenvironment improvement was able to restore a nearly normal haemopoiesis. We suggest that diphosphonate therapy may be of value in patients with AMM and increased bone turnover.

Aged↗
PubMed1994

Hunting the hemochromatosis gene: progress and problems.

Hereditary hemochromatosis (HFE) is an inherited recessive disorder which causes progressive iron overload. Homozygotes for the affected gene develop symptoms of parenchymal organ damage and especially liver cirrhosis in midlife. Early diagnosis is important in order to prevent symptoms. The protein responsible for the increased iron absorption is unknown. The tight association of the disease gene with HLA-A has been known for nearly 20 years, but its precise localization remains uncertain. Linkage and linkage disequilibrium analyses in different populations have focussed on two possible locations of the gene either very close to HLA-A, or at the telomeric site of 6p in the vicinity of the D6S105 marker.

Female↗