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Biomedical subjects

E Bertini

Publications and source records attributed to E Bertini.

At least 73 records · Page 4Linked to original sources
PubMed2000

A novel nonsense mutation (Q509X) in three Italian late-infantile neuronal ceroid-lipofuscinosis children.

We identified a novel nonsense CLN2 mutation (Q509X) in three Italian children with classical late-infantile neuronal ceroid lipofuscinosis (LINCL) from two unrelated families. The mutation introduced a premature stop codon in exon 12 of the CLN2 gene, resulting in a protein lacking the last 54 residues. Haplotype analysis suggested independent origin of the mutation in our families. The protein truncation test was employed to verify the functional consequences of the novel Q509X mutation. In Patient 1, the mutant alleles were transcribed but translated in a shorted peptide suggesting that the Q509X mutation is likely to interfere with CLN2p function. While expanding the list of genetic variants in LINCL, our findings represent the first molecular characterization of LINCL patients in South Europe.

Aminopeptidases↗
PubMed2000

Detection of mutations in the ALD gene (ABCD1) in seven Italian families: description of four novel mutations.

The study describes the mutations causing adrenoleukodystrophy in seven Italian families. Four missense mutations leading to amino acid substitutions, two frameshift mutations leading to a premature termination signal, and a splicing mutation were identified. Mutations 2014C>T (P543L), 2053A>G (Q556A), 673-674insCC, and 1874+1G>A are described for the first time in this report. Mutations 1638C>T (R418W), 1588G>A(R401Q), and 1801-1802delAG are already known to be link to ALD.

ATP Binding Cassette Transporter, Subfamily D, Mem↗
PubMed2000

Congenital muscular dystrophy associated with calf hypertrophy, microcephaly and severe mental retardation in three Italian families: evidence for a novel CMD syndrome.

We describe four Italian patients (aged 3, 4, 12, and 13 years ) affected by a novel autosomal form of recessive congenital muscular dystrophy. These patients were from three non-consanguineous families and presented an almost identical phenotype. This was characterized by hypotonia at birth, joint contractures associated with severe psychomotor retardation, absent speech, inability to walk and almost no interest in their surroundings. In addition, all patients had a striking enlargement of the calf and quadriceps muscles. Ophthalmologic examination revealed no structural ocular abnormalities in any of the children; one patient had severe myopia. In all cases a magnetic resonance imaging of the brain showed an abnormal posterior cranial fossa with enlargement of the cisterna magna and variable hypoplasia of the vermis of the cerebellum. Abnormality of the white matter was also present in all patients, in the form of patchy signal most evident in the periventricular areas. Serum CK was grossly elevated in all. The muscle biopsy from all cases showed dystrophic changes compatible with congenital muscular dystrophy. Immunofluorescence studies showed mild to moderate partial deficiency of laminin alpha 2 chain. Linkage analysis in the only informative family excluded the known loci for congenital muscular dystrophy, including laminin alpha 2 chain on chromosome 6q2, the Fukuyama congenital muscular dystrophy locus on 9q3 and the muscle-eye-brain disease on chromosome 1p3. We propose that this represent a novel severe variant of congenital muscular dystrophy, with associated central nervous system involvement.

Adolescent↗
PubMed2000

A novel SURF1 mutation results in Leigh syndrome with peripheral neuropathy caused by cytochrome c oxidase deficiency.

We report on a 5-year-old boy with clinical and neuroradiological evidence of Leigh syndrome and peripheral neuropathy. Skeletal muscle biopsy showed decreased cytochrome c oxidase stain. Ultrastructurally, the nerve biopsy showed a defect of myelination. Biochemical analyses of muscle homogenate showed cytochrome c oxidase deficiency (15% residual activity). SURF1 gene analysis identified a novel homozygous nonsense mutation which predicts a truncated surf1 protein.

Biopsy↗
PubMed2000

OXPHOS and mtDNA alterations in a family with spastic paraparesis.

OBJECTIVE: To study muscle biopsies in hereditary spastic paraparesis (HSP). METHODS: We analyzed oxidative phosphorylation activities and mtDNA in 3 individuals from an HSP family. RESULTS: We found histochemical evidence for mitochondrial proliferation and cytochrome c oxidase negative fibers. Biochemically, there was an important reduction of the activities of complexes I and IV in 3 patients. In addition, multiple mtDNA deletions (ranging 4.0-7.0 kb) were found in 2 cases by PCR but not by Southern blot. CONCLUSION: We suggest the use of a muscle biopsy when examining HSP patients. HSP can represent a disorder of nuclear-mitochondrial intercommunication.

Adult↗
PubMed2000

HyperCKemia as the only sign of McArdle's disease in a child.

An asymptomatic 13-year-old boy, who never complained of exercise intolerance or myalgia, was found to have markedly elevated serum creatine kinase (CK) levels during a routine check-up. General physical and neurologic examinations were normal. Surprisingly, histochemical and biochemical analysis of muscle showed myophosphorylase deficiency and genetic analysis showed that the patient was homozygous for the most common mutation encountered in McArdle's disease (R49X). This case illustrates the fuzzy correlation between molecular defect and clinical phenotype in patients with McArdle's disease, and suggests that a thorough study of the muscle biopsy is important in patients with idiopathic hyperCKemia for correct diagnosis and careful follow-up.

Adolescent↗
PubMed2000

Multi-minicore disease--searching for boundaries: phenotype analysis of 38 cases.

Multi-minicore disease (MmD) is a congenital myopathy morphologically defined by the presence of multiple small zones of sarcomeric disorganization and lack of oxidative activity ("minicores") in muscle fibers. The dinical expression of MmD is considered to be greatly variable, and the morphological lesions are nonspecific; therefore, its boundaries are poorly defined, and its molecular bases are not known. To better define the phenotypic characteristics of MmD, we analyzed a large series of 38 patients with multiple minicores in muscle fibers in the absence of any other potential cause. According to clinical features, 4 subgroups were identified. Most patients (30 cases) shared a common highly consistent phenotype marked by the axial predominance of muscle weakness and a high occurrence of severe respiratory insufficiency and scoliosis ("classical" form). Other forms were characterized by pharyngolaryngeal involvement and total lack of head control (2 cases), antenatal onset with arthrogryposis (3 cases), and slowly progressive weakness with marked hand amyotrophy (3 cases). Type 1 fiber predominance and hypotrophy as well as centrally located nuclei were found in every subgroup. MmD is thus phenotypically heterogeneous, but a typical recognizable phenotype does exist. This phenotype classification should be helpful when undertaking research into the molecular defects that cause MmD.

Biopsy↗
PubMed1999

A heterozygous splice site mutation in COL6A1 leading to an in-frame deletion of the alpha1(VI) collagen chain in an italian family affected by bethlem myopathy.

Bethlem myopathy is a mild neuromuscular disorder with proximal muscular weakness and early flexion contractures. It is an autosomal dominant disease due to mutations in type VI collagen genes. We found a T-->C substitution at the +2 position of COL6A1 intron 14 in a family, leading to skipping of exon 14 and an in-frame deletion of 18 amino acids in the triple-helical domain of the alpha1(VI) collagen chain. The deletion included a cysteine residue believed to be involved in the assembly of type VI collagen dimers intracellularly, prior to the protein secretion. Analysis of the affected fibroblasts showed that the shortened alpha1(VI) collagen chains were synthesized but not secreted by the cells and that the amount of type VI collagen microfibrils deposited by the cells was reduced. The results suggest that the clinical phenotype is due to a reduction in the level of type VI collagen in the extracellular matrix.

Adult↗
PubMed1999

Neurophysiologic follow-up of long-term dietary treatment in adult-onset adrenoleukodystrophy.

OBJECTIVE: To monitor the effects of dietary treatment in adult-onset adrenoleukodystrophy (ALD) by means of somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs). BACKGROUND: SEPs and MEPs have proved useful in revealing signs of progressively severe, central dying-back axonopathy in early stages of adult-onset ALD. METHODS: Eight patients with adult-onset ALD underwent clinical examination, brain and spine MRI, and SEP and MEP studies before and after 3 years of Lorenzo's oil dietary therapy. RESULTS: Before treatment, brain MRI was normal in five patients. Three of these patients had pure spinal SEP abnormalities and in the remaining two patients SEPs showed signs of involvement of both the spinal and cerebral somatosensory tracts. After treatment, the three patients with pure spinal abnormalities showed clinical and neurophysiologic worsening, whereas the two patients with a more advanced stage of disease (exhibited by SEPs) showed substantially unchanged clinical and neurophysiologic features. The patients with abnormal brain MRI at the onset of treatment showed clinical and neurophysiologic worsening. CONCLUSIONS: Lorenzo's oil therapy had no effect on patients with evidence of inflammatory brain lesions. Moreover, in patients without clear signs of inflammatory damage, this treatment does not modify significantly the natural course of the disease. However, because effective treatments should begin before the onset of severe neurologic symptoms, SEPs and MEPs should be considered to evaluate the effectiveness of other experimental treatments in the patient with a negative brain MRI.

Adrenoleukodystrophy↗
PubMed1999

Two novel missense mutations causing adrenoleukodystrophy in Italian patients.

The authors present two new missense mutations in exon 1 of the adrenoleukodystrophy (ALD) gene. The first, a C813T transition, results in the substitution Pro143 Ser in the third putative transmembrane domain of the adrenoleukodystrophy protein (ALDP) in an adult onset case. The second, a de novo C709T transition, results in a substitution Ser 108 Leu between the second and the third putative transmembrane segments, in a childhood case.

ATP Binding Cassette Transporter, Subfamily D, Mem↗
PubMed1999

A novel de novo mutation in the triple helix of the COL6A3 gene in a two-generation Italian family affected by Bethlem myopathy. A diagnostic approach in the mutations' screening of type VI collagen.

Bethlem myopathy is an autosomal dominant inherited disease producing a mild neuromuscular disorder, characterized mainly by muscular weakness and multiple joint contractures. Bethlem myopathy is caused by mutations in one of the three chains of collagen type VI. Here we report the clinical description and the molecular characterization of the defect in a two-generation Italian family in which a Gly-->Arg substitution disrupts the triple helix structure of the alpha 3 chain of collagen type VI, an ubiquitous glycoprotein of the extracellular matrix. In this family the identification of the mutation also allowed one to exclude the disease in the grandfather. It is noteworthy that the father of the proband carries a de novo mutation, the first described for Bethlem myopathy.

Adult↗
PubMed1998

A novel insertion mutation (A169i) in the CLN1 gene is associated with infantile neuronal ceroid lipofuscinosis in an Italian patient.

Infantile neuronal ceroid lipofuscinosis (INCL) is a progressive encephalopathy characterized by psychomotor deterioration, early visual loss, and an evanishing EEG. Mutations in the CLN1 gene encoding palmitoyl-protein thioesterase (ppt) have been reported in all Finnish INCL patients and in several non-Finnish North European patients. No cases have been contributed from the Mediterranean area thus far. We identified a single adenine insertion at nucleotide position 169 (A169i) in the CLN1 gene in a family in which the proband suffered from an INCL-like syndrome. The novel mutation was homozygous in blood from the proband, heterozygous in his healthy parents, and not found in control alleles. The mutation leads to an early stop codon resulting in an abnormal and truncated ppt protein. Our observations provide the first molecular characterization of an Italian INCL patient and expand the list of the known defects in INCL.

Brain↗
PubMed1998

X-linked adrenoleukodystrophy: first report of the Italian Study Group.

In this paper we report Italian data on X-linked adrenoleukodystrophy (ALD) collected from 1985 to 1997. This disease appears to be the most common of the peroxisomal disorders and is associated with a functional defect of the peroxisomal very long chain fatty acid (VLCFA) oxidation. In Italy 117 cases have been recognized, but many cases may be unrecognized due to the heterogeneous clinical manifestations that vary from mild to very severe forms. To control the devastating course of this disease two therapeutic approaches are under evaluation: bone marrow transplantation (BMT) and dietary treatment based on a mixture of glyceroyl trioleate (GTO) and glyceroyl trierucate (GTE). Our experience of 68 subjects submitted to dietary treatment shows that almost all patients with signs of cerebral involvement at the beginning of treatment worsened or died, patients with the milder form, adrenomyeloneuropathy (AMN), remained stable, while 4 of the 15 presymptomatic subjects developed neurological signs of the disease. In recent years a more accurate selection of patients and donors for BMT has given favourable results, but some strict criteria should be respected.

Adolescent↗