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A Morrone

Publications and source records attributed to A Morrone.

At least 37 records · Page 2Linked to original sources
PubMed2002

Two new mutations in children affected by partial biotinidase deficiency ascertained by newborn screening.

Mutation analysis performed on DNA from 6 Italian patients with partial biotinidase deficiency ascertained by newborn screening allowed the identification of two new mutations, c1211C > T (T404I) and a single base deletion c594delC. All patients were compound heterozygous for the D444H amino acid substitution showing that this mutation is also common in Italian patients affected by partial biotinidase deficiency.

Amidohydrolases↗
PubMed2002

A case of loiasis in Rome.

BACKGROUND: Owing to the increase of an immigrant population and of Italian citizens travelling for tourism or on business, it is nowadays possible to observe clinical pictures characteristic of tropical regions, often with indistinct symptoms. One of these is Loa loa infestation, or loiasis, a form of filariasis caused by Loa loa and transmitted by the Chrysops fly. We present the case of a male immigrant from Cameroon. Characteristic symptoms were intense xerosis, mostly of the third inferior part of the legs, intensely pruritic, with numerous lesions from scratching. No benefit was obtained by emollient topics, anti-acarus and systemic antihistamines. METHOD: Serum samples and Giemsa, haematoxylin, haematoxylin + Giemsa concentration-on-membrane stains, have evidenced the presence of Loa loa microfilariae. RESULTS: A diagnosis for L. loa (loiasis) infestation was made. CONCLUSIONS: At the beginning of the migration phenomenon, particularly from Africa, Italian physicians, especially dermatologists, were eagerly looking for 'tropical' diseases; this approach can be defined as 'Salgari's syndrome' from the name of the Italian novelist who, though never travelling out of Italy, had perfectly described environments and habits typical of far away countries. Now, conversely, we have to avoid the opposite approach of considering real tropical diseases as related to social or psychological difficult conditions.

Adult↗
PubMed2001

3-Hydroxy-3-methylglutaric aciduria in an Italian patient is caused by a new nonsense mutation in the HMGCL gene.

3-Hydroxy-3-methylglutaric aciduria is a rare autosomal recessive inborn error of metabolism caused by deficiency of the mitochondrial enzyme 3-hydroxy-3-methylglutaryl-CoA lyase (HMGCL). Up to now only a few mutations have been reported in the HMGCL gene. We report the first Italian patient, a female who presented metabolic acidosis at 3 days of age and then 3 months later. Analysis of urinary organic acids showed the excretion of 3-hydroxy-3-methylglutaric acid, 3-methylglutaconic acid, 3-methylglutaric acid, and 3-hydroxyisovaleric acid. A defect of HMGCL activity was suspected and then confirmed on cultured skin fibroblasts. Brain RM showed a diffuse mild abnormality of cerebral white matter in the periventricular regions, and the single voxel proton MRI spectroscopy showed abnormal peaks. In the patient's full-length HMGCL-cDNA a new c286C > T transition that leads to the stop codon Q96X was detected at the homozygous level. This mutation, that gives rise to a truncated protein, was confirmed in the patient's and also her parents' genomic DNA. The severe genetic lesion identified in the patient, which is in contrast with the mild clinical phenotype, stresses the importance of early diagnosis and therapy in HMGCL deficiency.

Brain↗
PubMed2000

beta-galactosidase gene mutations affecting the lysosomal enzyme and the elastin-binding protein in GM1-gangliosidosis patients with cardiac involvement.

GM1-gangliosidosis is a lysosomal storage disorder caused by deficiency of acid beta-galactosidase (GLB1). We report five new beta-galactosidase gene mutations in nine Italian patients and one fetus, segregating in seven unrelated families. Six of the eight patients with the infantile, severe form of the disease presented cardiac involvement, a feature rarely associated with GM1-gangliosidosis. Molecular analysis of the patients' RNA and DNA identified two new RNA splicing defects, three new and three previously described amino acid substitutions. Interestingly, all patients with cardiac involvement were homozygous for one of these mutations: R59H, Y591C, Y591N, or IVS14-2A>G. In contrast, all other patients were compound heterozygous for one of the following mutations: R201H, R482H, G579D, IVS8+2T>C. Although we could not directly correlate the presence of cardiac abnormalities with specific genetic lesions, the mutations identified in patients with cardiomyopathy fell in the GLB1 cDNA region common to the lysosomal enzyme and the Hbeta-Gal-related protein, also known as the elastin binding protein (EBP). Consequently, both molecules are affected by the mutations, and they may contribute differently to the occurrence of specific clinical manifestations.

Amino Acid Sequence↗
PubMed2000

Lymphocyte mRNA analysis of the ornithine transcarbamylase gene in Italian OTCD male patients and manifesting carriers: identification of novel mutations.

A new simple, non-invasive method using ornithine transcarbamylase (OTC) mRNA isolated from peripheral blood (PBL) or lymphoblastoid cell lines has been performed. This approach based on reverse transcription and nested PCR to obtain a double strand PBL OTC cDNA allowed the identification of genetic lesions in five Italian families affected by OTC deficiency (OTCD). In the PBL OTC mRNA two new mutations, T262K and W265L, have been detected in three unrelated male OTCD patients with mild symptoms. One known mutation, T264A, has been identified in one manifesting carrier. The known mutation E310X, detected on genomic DNA of another manifesting carrier, failed to be detected in her PBL OTC mRNA because of the presence of a STOP codon. All mutations have been confirmed in the patients' and their relatives' genomic DNA. In three patients the mutations have also been confirmed in the mRNA isolated from frozen liver biopsy. The T262K amino acid substitution has been detected in a male's PBL OTC mRNA at homozygous state while a heterozygous pattern has been detected at the genomic DNA level, suggesting that the patient is a somatic mosaic for this mutation. Here we show that PBL OTC mRNA analysis is useful to detect genetic lesions in male and female OTCD patients.

Cell Line, Transformed↗
PubMed2000

Immigration and health: the Italian National Focal Point experience.

This report is a description of the situation of migrant populations in Italy. It was written by a committed team of experts from public institutions, non-governmental organisations (NGO) and volunteer associations that for three years have been part of the Italian National Focal Point (NFP) within the European Project "AIDS & Mobility", which is being co-ordinated by the Netherlands Institute for Health Promotion and Disease Prevention (the Netherlands) and financed by the European Commission DG/V. This year the Italian National Focal Point, co-ordinated by the Telefono Verde AIDS of the Istituto Superiore di Sanità, has produced a second report (the first one was published in 1998) on health issues related to migrant populations. Besides providing an updated picture on the presence of foreigners in Italy, such report illustrates the present legislative situation within the sanitary area and some interventions regarding prevention, treatment and rehabilitation provided by each structure in the Italian NFP to foreign citizens. The initiatives carried out during the year 1999 by public institutions, NGO and volunteer associations are also reported in order to detect the psycho-social-sanitary needs of immigrants and target prevention programmes to their particular and specific needs.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Immigration and health: the Italian situation. Italian National Focal Point (NFP) of the AIDS & Mobility Project.

This report is a description of the situation of migrant populations in Italy. It was written as part of the European project "AIDS & Mobility", which is being co-ordinated by the Netherlands Institute for Health Promotion and Disease Prevention and financed by the European Union (EU). The report was written by the Italian National Focal Point (NFP) of the AIDS & Mobility Project, which consists of a committed team of experts from public institutions, non-governmental organizations, volunteer associations, and researchers from the Telefono Verde AIDS (National AIDS Help-line of Italy) of the Centro Operativo AIDS (COA, National AIDS Unit of Italy) of the Istituto Superiore di Sanità. The report illustrates the phenomenon of immigration in Italy, with demographic data (updated at 31 December 1997) on the presence of non-Italians and a review of the current laws pertinent to this phenomenon, with particular reference to health care laws. Moreover, epidemiological data on HIV/AIDS and on sexually transmitted diseases are provided, particularly as they relate to drug addiction and prostitution. Finally, following an accurate analysis of the situation and in light of the experience gained, the report includes proposals for identifying needs, objectives to pursue, and strategies to adopt, with respect to confronting the issue of immigration.

Emigration and Immigration↗
PubMed1997

RNA metabolism in myotonic dystrophy: patient muscle shows decreased insulin receptor RNA and protein consistent with abnormal insulin resistance.

Myotonic dystrophy is a dominantly inherited clinically variable multisystemic disorder, and has been found to be caused by heterozygosity for a trinucleotide repeat expansion mutation in the 3' untranslated region of a protein kinase gene (DM kinase). The mechanisms by which the expanded repeat in DNA results in a dominant biochemical defect and the varied clinical phenotype, is not known. We have recently proposed a model where disease pathogenesis may occur at the RNA level in myotonic dystrophy: the mutant DM kinase RNA with the expansion mutation may disrupt cellular RNA metabolism in some general manner, as evidenced by defects in RNA processing of the normal DM kinase gene in heterozygous patients (dominant negative RNA mutation). Here we further test this hypothesis by measuring RNA metabolism of other genes in patient muscle biopsies (nine adult onset myotonic dystrophy patients, two congenital muscular dystrophy patients, four normal controls, and four myopathic controls). We focused on the insulin receptor gene because of the documented insulin resistance of DM patients. We show that there is a significant decrease in insulin receptor RNA in both total RNA and RNA polyA+ pools relative to normal and myopathic control muscles (P < 0.002), measured relative to both dystrophin RNA and muscle sodium channel RNA. We also show reductions in insulin receptor protein. Our results reinforce the concept of a generalized RNA metabolism defect in myotonic dystrophy, and offer a possible molecular mechanism for the increased insulin resistance observed in many myotonic dystrophy patients.

Adolescent↗
PubMed1997

Asymptomatic dystrophinopathy.

A 4-year-old girl was referred for evaluation for a mild but persistent serum aspartate aminotransferase (AST) elevation detected incidentally during routine blood screening for a skin infection. Serum creatine kinase activity was found to be increased. Immunohistochemical study for dystrophin in her muscle biopsy showed results consistent with a carrier state for muscular dystrophy. Molecular work-up showed the proposita to be a carrier of a deletion mutation of exon 48 of the dystrophin gene. Four male relatives also had the deletion mutation, yet showed no clinical symptoms of muscular dystrophy (age range 8-58 yrs). Linkage analysis of the dystrophin gene in the family showed a spontaneous change of an STR45 allele, which could be due to either an intragenic double recombination event, or CA repeat length mutation leading to identical size alleles. To our knowledge, this is the first documentation of an asymptomatic dystrophinopathy in multiple males of advanced age. Based on molecular findings, this family would be given a diagnosis of Becker muscular dystrophy. This diagnosis implies the development of clinical symptoms, even though this family is clearly asymptomatic. This report underscores the caution which must be exercized when giving presymptomatic diagnoses based on molecular studies.

Adolescent↗
PubMed1996

Early-infantile galactosialidosis: clinical, biochemical, and molecular observations in a new patient.

Few patients with the early-infantile form of galactosialidosis have been described to date. Presented here is the first Italian case. Fetal hydrops was detected by ultrasound at week 24 of gestation. At birth, the infant presented with hypotonia, massive edema, a flattened coarse facies, telangiectasias, and hepatosplenomegaly, but no dysostosis multiplex. The patient died 72 days postpartum. Excessive sialyloligosaccharides in urine, as well as vacuolation of lymphocytes and eosinophilic granulocytes in peripheral blood, were indicative of a lysosomal storage disease. In the patient's fibroblasts, both alpha-neuraminidase and beta-galactosidase activities were severely reduced, and cathepsin A activity was < 1% of control levels, confirming the biochemical diagnosis of galactosialidosis. However, in contrast to previously reported early-infantile cases, a normal amount of protective protein/cathepsin A mRNA was detected on Northern blots. This mutant transcript was translated into a precursor protein that was not processed into the mature enzyme and lacked both protective and catalytic activities.

Carboxypeptidases↗
PubMed1996

Molecular and biochemical analysis of protective protein/cathepsin A mutations: correlation with clinical severity in galactosialidosis.

Mutations in the gene encoding lysosomal protective protein/cathepsin A (PPCA) are the cause of the lysosomal disorder galactosialidosis (GS). Depending on age of onset and severity of the symptoms, patients present with either an early infantile (EI), a late infantile (LI), or a juvenile/adult (J/A) form of the disease. To study genotype-phenotype correlation in this disorder, we have analyzed the mutations in the PPCA gene of eight clinically different patients. In two EI and one J/A patient, we have identified four novel point mutations (Val104Met, Leu208Pro, Gly411Ser and Ser23Tyr), that prevent phosphorylation and, hence, lysosomal localization and maturation of the mutant precursors. Two amino acid substitutions (Phe412Val and Tyr221Asn) are shared by five LI patients. These mutations appear to be pathognomonic for this phenotype, and determine the clinical outcome depending on whether they are present together or in combination with other mutations. The latter include a single base deletion and a novel amino acid change (Met378Thr), which generates an additional glycosylation site. Within the LI group, patients carrying the Phe412Val mutation are clinically more severe than those with the Tyr221Asn substitution. This is in agreement with the biochemical behavior of the Asn221-mutant protein, that is, like the Phe412Val protein, phosphorylated, routed to lysosomes and proteolytically processed, but its intralysosomal stability is intermediate between that of wild-type PPCA and Val412-PPCA. Overall, these results may explain the clinical heterogeneity observed in GS patients and may help to correlate mutant allelic combinations with specific clinical phenotypes.

Alleles↗
PubMed1995

An X:autosome translocation stabilizes truncated dystrophin: implications for lack of truncated dystrophins in Duchenne muscular dystrophy.

We report a 5-year-old girl with clinical symptoms of typical Duchenne muscular dystrophy in males. The girl showed dramatic elevations of serum creatine kinase, and muscle biopsy histopathology consistent with a severe dystrophic myopathy. Cytogenetic analysis revealed an X:22 translocation (46,X,t [X;22] [p21.2;11.2]). Dystrophin immunofluoresence studies showed strong membrane immunostaining of dystrophin with antibodies directed against the amino terminus of the protein, but vastly reduced immunostaining with carboxyl-terminal antibodies. Immunoblot studies showed a major immunoreactive protein of approximately 350 kDa at approximately 20% levels. Nested RT-PCR analysis of the dystrophin mRNA in the patient's muscle showed the RNA to be positive for primers covering the first 85% of the dystrophin coding sequence, and negative for the carboxyl-terminal 15%. Taken together, our data suggests that the translocation breakpoint occurs towards the 3' end of the gene. The translocated dystrophin gene is still expressed into a truncated dystrophin protein associated with the plasma membrane. Our results are consistent with the translocation resulting in a more stable abnormal dystrophin mRNA.

Antibodies, Monoclonal↗
PubMed1994

Insertion of a T next to the donor splice site of intron 1 causes aberrantly spliced mRNA in a case of infantile GM1-gangliosidosis.

The lysosomal storage disorders GM1-gangliosidosis and Morquio B syndrome are caused by a complete or partial deficiency of acid beta-galactosidase. Here, we have characterized the mutation segregating in a family with two siblings affected by the severe infantile form of GM1-gangliosidosis. In total mRNA preparations derived from the patients' fibroblasts at least two aberrantly spliced beta-galactosidase transcripts (1 and 2) have been identified. Both transcripts contain a 20 nucleotide (nt) insertion derived from the 5' end of intron 1 of the beta-galactosidase gene. Furthermore, in transcript 2 sequences encoded by exon II are deleted during the splicing process. Comparison of the 20-nt insertion with wild-type intronic sequences indicated that in the genomic DNA of the patients an extra T nucleotide is present immediately downstream of the conserved GT splice donor dinucleotide of intron 1. Both patients are homozygous for the T nucleotide insertion. We propose that this single base insertion is the mutation responsible for aberrant splicing of beta-galactosidase pre-mRNA, giving rise to transcripts that cannot encode a normal protein.

Base Sequence↗
PubMed1994

Expression of stromelysin 3 and tissue inhibitors of matrix metallo-proteinases, TIMP-1 and TIMP-2, in rheumatoid arthritis.

Rheumatoid hyperplastic synovial lining cells and sublining fibroblasts are known to produce, in vivo and in vitro, matrix metallo-proteinases which degrade extracellular matrix components of joints. We have studied by immunohistochemistry and in situ hybridization the presence of matrix metallo-proteinase stromelysin 3 and its potential inhibitors TIMP-1 and TIMP-2 in 5 cases of normal synovia, 5 cases of chronic synovitis and 12 cases of rheumatoid arthritis. Few hyperplastic synoviocytes and some sparse fibroblasts have been found to produce stromelysin 3 in all rheumatoid arthritis and 2 chronic synovitis. Stromelysin 3 seems to have a limited role in the destructive process of extracellular matrix. TIMP-1 and TIMP-2 were largely expressed principally in hyperplastic synoviocytes and in endothelial cells of all rheumatoid synovitis and 2 chronic synovitis. These findings plead for a balance between matrix metallo-proteinases and their inhibitors in these inflammatory lesions.

Arthritis, Rheumatoid↗
PubMed1994

Antioxidant status in the blood of patients with active vitiligo.

We have previously reported that patients with active vitiligo (AVP) have elevated urinary levels of catecholamine metabolites, such as homovanillic and vanilmandelic acids, irrespective of the form of the disease (acrofacial, segmental, generalized). We have suggested that abnormal release of catecholamines from autonomic nerve endings might play an etiological role in the onset and development of vitiligo through an overproduction of toxic (oxy)radicals in the microenvironment of melanocytes in the affected areas. In the present study we have investigated whether this suggested increase in radicals might be associated with an oxidative stress in the blood of AVP. We have analyzed by gas-chromatography mass-spectrometry, by high pressure liquid chromatography, by spectrophotometry plasma levels of vitamin E (Vit E), lipoperoxides (LIP), and polyunsaturated fatty acids of phospholipids (PL-FA), erythrocyte reduced glutathione (GSH), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) activities in 62 patients affected with different forms of active vitiligo (acrofacial, segmental, generalized) and in 60 age-matched controls. Our results show that blood levels of Vit E, SOD, GSH, GSH-Px activity, LIP and PL-FA in AVP were not significantly different from those of healthy age matched controls, indicating that melanocyte damage in vitiligo is not linked with a generalized oxidative stress.

Adult↗
PubMed1993

[Chronic urticaria-macroglobulinemia (Schnitzler syndrome): developing to IgM myeloma. Apropos of a case].

Schnitzler's syndrome has been described in 1972. It associates a chronic urticaria with leukocytoclastic vasculitis, a macroglobulinemia, bone pains, hyperostosis. In the twenty three cases reported, the evolution is benign but three patients including the princeps case developed a Waldenström's disease or a lymphoplasmocytic lymphoma. We present the case of one patient, aged 65, with Schnitzler's syndrome, who, after 6 years evolution, presents a IgM myeloma. Schnitzler's syndrome appeared as a pre-hemopathic state which has to be taken care of regularly and for a long time.

Adrenal Cortex Hormones↗