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Biomedical subjects

A Meloni

Publications and source records attributed to A Meloni.

At least 19 recordsLinked to original sources
PubMed2005

Two novel mutations of the AIRE protein affecting its homodimerization properties.

We report two novel mutations, c.230T>C (p.F77S) and c.64_69del (p.V22_D23del) within the HSR domain of the AIRE protein in two patients of Italian descent affected by APECED. Both mutations were found in the compound heterozygous state respectively with c.994+5G>T and c.232T>A (p.W78R). With the two-hybrid assay in the yeast system we found that constructs containing the two mutations fail to interact with the wild-type protein. These findings indicate that both mutations negatively affected the homodimerization properties of the AIRE protein, thereby leading to a defective function.

Adult↗
PubMed2002

Clinicopathological features of genetically confirmed Danon disease.

BACKGROUND: Danon disease is due to primary deficiency of lysosome-associated membrane protein-2. OBJECTIVE: To define the clinicopathologic features of Danon disease. METHODS: The features of 20 affected men and 18 affected women in 13 families with genetically confirmed Danon disease were reviewed. RESULTS: All patients had cardiomyopathy, 18 of 20 male patients (90%) and 6 of 18 female patients (33%) had skeletal myopathy, and 14 of 20 male patients (70%) and one of 18 female patients (6%) had mental retardation. Men were affected before age 20 years whereas most affected women developed cardiomyopathy in adulthood. Muscle histology revealed basophilic vacuoles that contain acid phosphatase-positive material within membranes that lack lysosome-associated membrane protein-2. Heart transplantation is the most effective treatment for the otherwise lethal cardiomyopathy. CONCLUSIONS: Danon disease is an X-linked dominant multisystem disorder affecting predominantly cardiac and skeletal muscles.

Adolescent↗
PubMed2002

A novel splicing defect (IVS6+1G>T) in a patient with pseudovitamin D deficiency rickets.

A 15-month-old boy with severe rickets, that by clinical analysis was diagnosed as affected by hereditary pseudovitamin D deficiency rickets (PDDR), was evaluated for mutations in the 25OHD3 1alpha-hydroxylase gene. Molecular analysis showed a double heterozygous state for a novel splicing mutation in the invariant dinucleotide of the donor site of IVS6 and a 7 nucleotide insertion in the exon 8, which is common in different ethnical backgrounds.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed2001

Symptoms and neurophysiological picture of carpal tunnel syndrome in pregnancy.

OBJECTIVE: To evaluate the incidence of carpal tunnel syndrome (CTS) in pregnancy through a validated and multiperspective assessment of CTS. METHODS: During 2000, the Italian CTS study group focussed on the occurrence of CTS in women during the final stages of pregnancy, enrolled in 7 Italian centers. In addition to the physician-centered and neurophysiologic traditional evaluations, we used a validated patient-oriented measurement to obtain more comprehensive and consistent data for severity of symptoms and functional impairment. RESULTS: In our study, CTS was clinically diagnosed in more than half of women (62%). Neurophysiological evaluation provided diagnosis of CTS in around half of women (43% were positive in one hand at least). Our study provides evidence, reported here for the first time, of a correlation between edema and neurophysiological picture. Similarly, our study provides a correlation between validated patient-oriented measurement and edema. Moreover, a significant correlation between a negative trend (subjectively assessed) and smoking and alcohol consumption was observed. CONCLUSIONS: Our observations confirm that the edema of the tissues in the carpal tunnel could induce a mechanical compression of the nerve. Moreover, our data suggest that smoking and alcohol consumption have a negative role in the evolution of the syndrome probably due to impairment of the microcirculation.

Adult↗
PubMed2001

Allelic loss analysis by capillary electrophoresis: an accurate, automated method for detection of deletions in solid tumors.

In this report, we describe a fast and accurate capillary electrophoresis, PCR-based method for detecting loss of allelic heterozygosity in solid tumor samples. This automated method requires small sample sizes, and data can be obtained in less than 15 min. The method is particularly powerful for uncovering deletions in tumor sample preparations containing significant normal tissue contamination.

Chromosomes, Human, Pair 7↗
PubMed2000

Peroneal mononeuropathy: predisposing factors, and clinical and neurophysiological relationships.

The most common mononeuropathy in the lower extremity involves the nerve. We retrospectively evaluated the etiological predisposing factors and clinical-neurophysiological features of 36 patients affected by peroneal mononeuropathy (PM). In 30 patients, a clear predisposing factor was identified. PM was more frequently perioperative (11 cases), associated with axonal involvement. Unexpectedly, PM was not only due to surgery close to the peroneal region, but was mostly associated with hip surgery and, rarely, with thoracic-abdominal surgery. A postural predisposing factor of PM was also frequently observed, usually associated with a pure conduction block. Conversely, most patients with bedridden predisposing factor presented axonal involvement, which was rarely associated with conduction block. In 25 of 36 PM cases, a long-term follow-up lead to an improvement (12 cases) or to good recovery (13 cases) of PM. In conclusion, our study shows that: (1) in most PM cases it is possible to identify a predisposing factor; (2) there is a good correlation between predisposing factor and neurophysiological involvement, and (3) PM usually has usually a good prognosis.

Adolescent↗
PubMed1999

Trisomies 8 and 20 characterize a subgroup of benign fibrous lesions arising in both soft tissue and bone.

Trisomy 8 and trisomy 20 are nonrandom aberrations in desmoid tumors. The presence of these trisomies in related benign fibrous lesions of bone has not been previously addressed. In this study, 22 specimens from 19 patients diagnosed with desmoid tumor, desmoplastic fibroma, periosteal desmoid tumor, osteofibrous dysplasia, or fibrous dysplasia were examined by cytogenetic analysis of short-term cultures and bi-color fluorescence in situ hybridization of cytological touch preparations or paraffin-embedded tissue with centromeric probes for chromosomes 8 and 20. Trisomy 8 and trisomy 20 were detected by molecular cytogenetic methodologies in 15 specimens, including 10 primary bone lesions. Traditional cytogenetic analysis revealed trisomy 8 in two cases of osteofibrous dysplasia. Our findings demonstrate that trisomy 8 and trisomy 20 are also nonrandom aberrations in histologically similar, but clinically distinct, benign fibrous lesions of bone.

Adolescent↗
PubMed1998

A common mutation in Sardinian autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy patients.

Autoimmune polyendocrinopathy-candidiasisectodermal dystrophy (APECED; also called APS-1,) is a rare autosomal recessive disorder that is more frequent in certain isolated populations. It is characterized by two of the three major clinical symptoms that may be present: Addison's disease, and/or hypoparathyroidism and/or chronic mucocutaneous candidiasis. We have recently identified the gene for APECED, which we termed AIRE (for autoimmune regulator). AIRE is expressed in thymus, lymph nodes and fetal liver, and encodes a protein with two putative zinc fingers and other motifs suggestive of a transcriptional regulator. Seven mutations have been described to date, including R257X, the predominant Finnish and northern Italian APECED allele, which has also been observed in other patients of diverse origin on different haplotypes. A 13-bp deletion (1094-1106del) has also been observed in several patients of different geo-ethnic origin. The other described mutations appear to be rare. We present mutational analyses of the AIRE gene in ten Sardinian APECED families and show that there is a mutation, R139X, associated with one predominant haplotype unique to the Sardinian patients (18/20 independent alleles). The carrier frequency of R139X in Sardinia is 1.7%, giving an estimated population frequency of APECED of 1/14,400. Using linkage disequilibrium data, the estimated age of the R139X mutation is between 20 and 25 generations. A previously described 13-bp deletion was also observed on an allele of one patient. The identification of a single common Sardinian APECED mutation will facilitate its genetic diagnosis. Given the carrier frequency of R139X in the Sardinian population, AIRE may be implicated in the pathogenesis of other autoimmune diseases in the Sardinian population, particularly those affecting the endocrine system.

DNA Mutational Analysis↗
PubMed1998

Two cytochromes P450 are major hepatocellular autoantigens in autoimmune polyglandular syndrome type 1.

BACKGROUND & AIMS: Liver disease has been described in 10%-15% of patients with autoimmune polyglandular syndrome type 1 (APS-1). After the discovery of cytochrome P450 1A2 (CYP1A2) as a hepatocellular autoantigen in liver-kidney microsomal autoantibody (LKM)-positive patients with APS-1, the investigation of antiliver antibodies was extended to 11 Sardinian patients with APS-1. METHODS: Indirect immunofluorescence and Western blotting analysis were performed to study the antiliver antibodies. RESULTS: Immunofluorescence revealed LKM antibodies in 3 patients with APS-1, 1 of whom died of fulminant hepatitis. Western blotting showed a liver microsomal protein band of approximately 51 kilodaltons in the LKM-positive sera of these 3 patients. Western blotting performed with recombinant cytochrome P450 enzymes allowed the identification of CYP2A6 as a specific target antigen. CONCLUSIONS: LKM antibodies in APS-1 sera are specifically directed against CYP1A2 or CYP2A6, but their diagnostic and prognostic significance for liver disease remain to be determined.

Adult↗
PubMed1997

A homozygous nonsense mutation of the human growth hormone receptor gene in a Sardinian boy with Laron-type dwarfism.

Laron-type dwarfism (LTD) is an autosomal recessive disorder due to mutations in the GH receptor (GHR) gene. We report the case of a Sardinian boy affected by LTD in which we found by direct genomic sequencing a nonsense mutation in the fourth exon of the GHR gene (R43X) that determines a premature termination in the protein translation process. As the result of the absence of the extracellular portion of the GHR this patient had undetectable GH binding protein. This molecular defect is identical to that observed in other patients with LTD of mediterranean origin.

Base Sequence↗
PubMed1997

Molecular analysis of patients of Sardinian descent with Crigler-Najjar syndrome type I.

This study reports the molecular characterisation of the bilirubin UDP-glucuronosyl-transferase gene (UGT1) in a group of patients of Sardinian descent with Crigler-Najjar syndrome type I and their relatives. Sequence analysis of both UGT1A exon 1 and common exons 2-5 was performed in all patients, leading to the detection of AF170 and a novel mutation (470insT), both residing in UGT1A exon 1. All but two heterozygotes for the AF170 mutation showed normal serum bilirubin levels. These two subjects were also heterozygous for the sequence variation A(TA)7TAA in the promoter region of the UGT1A gene.

Adolescent↗
PubMed1997

Cytochrome P450 1A2 is a hepatic autoantigen in autoimmune polyglandular syndrome type 1.

Autoantibodies directed against proteins of the adrenal cortex and the liver were studied in 88 subjects of Sardinian descent, namely six patients with autoimmune polyendocrine syndrome type 1 (APS1), 22 relatives of APS1 patients, 40 controls with other autoimmune diseases, and 20 healthy controls. Indirect immunofluorescence, using tissue sections of the adrenal cortex, revealed a cytoplasmatic staining pattern in 4 of 6 patients with APS1. Western blotting with adrenal mitochondria identified autoantigens of 54 kDa and 57 kDa, Western blotting with placental mitochondria revealed a 54-kDa autoantigen. The 54-kDa protein was recognized by 4 of 6 patients with APS1 both in placental and adrenal tissue, whereas the 57-kDa protein was detected only by one serum. Using recombinant preparations of cytochrome P450 proteins, the autoantigens were identified as P450 scc and P450 c17. One of six APS1 patients suffered from chronic hepatitis. In this patient, immunofluorescence revealed a centrolobular liver and a proximal renal tubule staining pattern. Western blots using microsomal preparations of human liver revealed a protein band of 52 kDa. The autoantigen was identified as cytochrome P450 1A2 by use of recombinant protein preparations. P450 1A2 represents the first hepatic autoantigen reported in APS1. P450 1A2 usually is not detected by sera of patients with isolated autoimmune liver disease and might be a hepatic marker autoantigen for patients with APS1.

Adolescent↗
PubMed1996

Analysis of 3p allelic loss in papillary and nonpapillary renal cell carcinomas. Correlation with tumor karyotypes.

Nonpapillary renal cell carcinomas (RCCs) are characterized by deletions of the short arm of chromosome 3 (3p) and papillary RCCs by increased numbers of selected chromosomes. Although recent molecular genetic studies have reported some papillary RCCs to show loss of heterozygosity (LOH) on 3p, a 3p deletion has not been demonstrated in a papillary RCC by karyotype analysis. To investigate this apparent discrepancy between molecular methods and chromosomal changes in the genetic evaluation of RCC, a series of 13 papillary and nonpapillary RCCs was investigated for 3p LOH by PCR-based restriction fragment length polymorphism (PCR-RFLP) analysis and for 3p and 3q LOH by microsatellite analysis. Karyotypes were obtained in six cases. Loss of 3p but not of 3q alleles was found in 8 of 10 nonpapillary RCCs. The region of overlapping deletion was 3p14--p21, and in six cases the deletion involved 3pter loci. One papillary RCC displayed 3p and 3q LOH, but the tumor had two morphologically normal chromosomes 3 and several trisomies. This indicated that nondisjunction of a chromosome from one parent compensated a whole chromosome loss from the other parent during tumor development. LOH in this papillary RCC constituted a reduction of chromosome 3 alleles to homozygosity, but the karyotype change, consisting of an increased number of whole chromosomes and an absence of a structural chromosome 3 abnormality, is regarded as being more characteristic of papillary than nonpapillary RCC.

Alleles↗
PubMed1995

A modified spectroscopic method for the determination of the transbilayer distribution of phosphatidylethanolamine in soya-bean asolectin small unilamellar vesicles.

A spectroscopic kinetic approach for determining the relative concentrations of phosphatidylethanolamine (PE) exposed on the external and internal layers of small unilamellar vesicles (SUVs) used as a model system and prepared by sonication of purified soya-bean asolectin is proposed, based on the use of 2,4,6-trinitrobenzenesulphonic acid (TNBS) and N-succinimidyl 3-(2-pyridyldithio)propionate (SPDP). The known reactions between PE and TNBS and/or SDPD were used, separately or in combination, to derivatize PE in preformed vesicles. We have observed that mixing SUVs with excess TNBS results in a biphasic time course. Kinetic analysis of the data supports the conclusion that external PE is rapidly derivatized (fast phase) with a half-time of 2 min. In the next (slow) phase (half-time 70 min), TNBS permeates the vesicle membrane and also reacts with PE molecules facing the internal liposomal compartment. Under the experimental conditions chosen, SPDP reacted with only the external PE molecules. The reaction of SUVs first derivatized with SPDP and then with TNBS further demonstrates that the two phases, observed with TNBS, are due to modification of external and internal PE. Approx. 30% of PE was found to be facing the external bulk phase, thus confirming the asymmetric distribution of the molecules in SUVs. The maximum number of thiol arms covalently linked by means of SPDP modification of PE on the surface of a single liposome was estimated at about 10(2).

Cross-Linking Reagents↗