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Biomedical subjects

A Morrone

Publications and source records attributed to A Morrone.

At least 19 recordsLinked to original sources
PubMed2006

An unusual clinical and biochemical presentation of ornithine transcarbamylase deficiency in a male patient.

We report a male patient with a history of recurrent idiopathic vomiting, normal plasma ammonia and glutamine concentrations in acute phase, who died at 3 years of age. Ornithine transcarbamylase deficiency was diagnosed after detecting elevated urinary orotate concentrations in a sample collected just before death, and the diagnosis was confirmed by DNA analysis.

Amino Acid Metabolism, Inborn Errors↗
PubMed2006

Genetic and biochemical approach to early prenatal diagnosis in a family with mut methylmalonic aciduria.

Genetic and biochemical prenatal diagnosis was performed at 11 weeks of gestation in a family with a proband affected by mut methylmalonic aciduria (MMA) and homozygotes for the MUT gene c.643G>A (p.Gly215Ser) mutation. Both chorionic villus and amniotic fluid samples were used. The presence of high levels of methylmalonic acid and propionylcarnitine determined by gas chromatography/mass spectrometry and LC/MS/MS analysis, respectively, and the identification of the p.Gly215Ser at a homozygous level in foetal DNA allowed a certain, rapid and early diagnosis. To our knowledge, this is the first mut MMA prenatal diagnosis carried out by genetic and biochemical approach.

Amino Acid Metabolism, Inborn Errors↗
PubMed2006

Simultaneous occurrence of linear scleroderma and homolateral segmental vitiligo.

Localized scleroderma and vitiligo only rarely have been reported to occur simultaneously. Here we report a case of a 21 year old man affected with both linear scleroderma of the left upper limb and homolateral segmental vitiligo of the trunk. Since the two diseases appeared during the same period, involved the same side of the body and their progression paralleled, a possible non-coincidental association between these two diseases is discussed.

Abdomen↗
PubMed2005

Successful prenatal molecular diagnosis of carbamyl-phosphate synthetase I deficiency in two at-risk pregnancies.

We report the two first prenatal diagnoses in an Italian family with a proband affected by neonatal carbamyl-phosphate synthetase I deficiency in which molecular analysis identified V457G and Q810R amino acid substitutions. We performed a prenatal diagnosis on genomic DNA isolated from chorionic villus and amniotic fluid samples collected at 13 weeks of gestation. In the first pregnancy, the fetus was compound heterozygous for the mutations and termination of pregnancy was elected. The genetic lesions were also confirmed on genomic DNA isolated from the fetus's liver and skin fibroblasts. A few months later, we performed a second prenatal diagnosis in this family. The second fetus was heterozygous for the wild-type alleles. The pregnancy was continued and a girl was born at 41 weeks of gestation. We have confirmed the wild-type state on the baby's DNA.

Amniocentesis↗
PubMed2004

Four novel mutations in patients from the Middle East with the infantile form of GM1-gangliosidosis.

GM1-gangliosidosis is a lysosomal storage disorder caused by a deficiency of beta-galactosidase. It is mainly characterized by progressive neurodegeneration and in its most severe infantile form it leads to death before the age of four. We have performed molecular analysis of five patients with the infantile form of GM1-gangliosidosis originating from the Middle East (two from Saudi Arabia and three from the United Arab Emirates). We have identified four novel mutations and one previously reported mutation in the GLB1 gene. The first novel mutation found in the homoallelic state in a patient from Saudi Arabia, is a c.171C>G transversion in exon 2 which creates a premature stop codon. Northern blot analysis in fibroblasts from the patient showed no mRNA and expression studies in COS-1 cells showed complete absence of the 85kDa precursor protein and no catalytic activity. The second novel mutation is a splicing error in intron 2, c.245+1G>A. This mutation was found in the heteroallelic state in a patient from Saudi Arabia, the second mutation being the previously described c.145C>T mutation. The third novel mutation is a missense mutation in exon 4, c.451G>T, found in the homoallelic state in a patient from the United Arab Emirates. Expression studies of this mutation in COS-1 cells showed complete absence of the 85kDa precursor protein and no catalytic activity. The fourth novel mutation is a splicing mutation in intron 8, c.914+4A>G, found in the homoallelic state in two siblings from the United Arab Emirates. This study has revealed genetic heterogeneity of the beta-galactosidase deficiency in the Arabic population [corrected]

Animals↗
PubMed2003

Structural organization of the human carbamyl phosphate synthetase I gene (CPS1) and identification of two novel genetic lesions.

Carbamyl Phosphate Synthetase I deficiency (CPSID) is a rare autosomal recessive urea cycle disorder usually characterized by potentially lethal neonatal hyperammonemia. The large (5215 bp) CPS1-cDNA, expressed only in liver and epithelial cells of intestinal mucosa, has been cloned. Until now the CPS1 genomic organization was unknown. Taking advantage of the phylogenetic lineage between the CPS1 gene of Homo sapiens and Rattus norvegicus, we determined the intron-exon organization of the human CPS1 gene. Starting from the ATG codon, the CPS I gene is organized in 38 exons spanning from 50bp to 200 bp. We also report the molecular studies on an Italian patient affected by neonatal CPSD. Two novel genetic lesions (c.1370T>G and c.2429A>G) that lead to the novel amino acid substitutions V457G and Q810R, and the known N1406T polymorphism, were detected in the patient's CPS1 RNA and in genomic DNA isolated from peripheral blood lymphocytes. The characterization of the CPS1 genomic organization will allow the identification of the genetic lesions of CPSD patients, the detection of carriers, better genetic counseling and a more certain, less invasive method of prenatal diagnosis.

Amino Acid Substitution↗
PubMed2003

Development and validation of a radioligand binding assay to measure insulin specific IgG subclass antibodies in human serum.

The objective was to develop and validate a radioligand binding assay for insulin antibodies (IABs) of the IgG1, IgG2, IgG3, and IgG4 subclasses in human serum. The validation studies focused on determining specificity, capacity, linearity, sensitivity, and precision of each assay. It was seen that our assay for IAB IgG subclasses is specific and has sufficient capacity to measure each of the subclasses in human serum. Moreover, the linear region and limits of detection and quantitation for each assay are clearly determined.

Antibody Specificity↗
PubMed2002

Clinical findings and biochemical and molecular analysis of four patients with holocarboxylase synthetase deficiency.

Holocarboxylase synthetase (HLCS) deficiency (HLCSD) is a rare autosomal recessive disorder of biotin metabolism. HLCS catalyzes the biotinylation of the four human biotin-dependent carboxylases. Using the newly available human genomic sequence, we report the map of HLCS genomic structure and the predicted exon/intron boundaries. Moreover, the molecular studies of four patients (two Italians, one Iranian, and one Australian) affected by HLCS deficiency are here reported. The clinical findings, the age of onset, and response to biotin treatment differed between our patients. The diagnosis was made by organic acid analysis and confirmed by enzymatic analysis in three patients. Six mutations in the HLCS gene were identified, including two novel (N511K and G582R) and four known missense mutations (L216R, R508W, V550M, and G581S). Five of the mutations are localized within the HLCS biotin-binding domain, whereas the L216R amino acid change is located in the N-terminal region outside of the putative biotin-binding domain. This mutation, previously reported in a heterozygous state, was detected for the first time in a patient with homozygous status. The patient's severe clinical phenotype and partial responsiveness to biotin support a genotype-phenotype correlation through the involvement of residues of the N-terminal region in a substrate specificity recognition or regulation of the HLCS enzyme.

Acidosis↗
PubMed2002

Genetic analysis in nine unrelated Italian patients affected by OTC deficiency: detection of novel mutations in the OTC gene.

Ornithine transcarbamylase deficiency (OTCD) is an X-linked urea cycle disorder due to a defect of the mithocondrial enzyme ornithine transcarbamylase (OTC). Genetic analysis in nine unrelated Italian patients affected by OTCD (one male patient and eight female manifesting carriers) led to the detection of three novel mutations and six previously reported mutations in the OTC gene. The analysis was performed by direct sequencing of OTC cDNA, OTC exons, and intron-exon boundaries and enzymatic restriction analysis on the patients' genomic DNA and total RNA isolated from peripheral blood lymphocytes. In the male patient the new mutation S132P due to the nucleotide change c.394T>C was identified. In a manifesting carrier the nucleotide change c.292G>A that leads to the novel amino acid substitution E98K was identified; this mutation is close to the OTC protein's carbamyl phospate binding site. In another manifesting carrier the OTC cDNA analysis revealed the normally spliced transcript and an aberrant transcript with an insertion of two nucleotides (c.77-78insAG). In the patient's genomic DNA we identified a new transvertion IVS1-3C>G at the heterozygous state; this nucleotide change generates a new splice acceptor site in intron 1 that induces an RNA splicing defect. This insertion causes a frame shift in OTC cDNA ORF and leads to a premature stop codon. The previously described mutations N161S, R141Q, T178M, R92X, A208T, M268T were identified in the other six manifesting carriers.

Alleles↗
PubMed2002

Two novel genetic lesions and a common BH4-responsive mutation of the PAH gene in Italian patients with hyperphenylalaninemia.

Hyperphenylalaninemia (HPA), due to a deficiency of phenylalanine hydroxylase (PAH) enzyme, is caused by mutations in the PAH gene. Molecular analysis in 23 Italian patients with PAH deficiency identified two novel (P281R, L287V) and 20 previously described genetic lesions in the PAH gene. The detection of the A403V amino acid substitution in combination with null mutations in patients with BH4-responsive PAH deficiency leads us to correlate it with BH4 responsiveness.

DNA Mutational Analysis↗