Neurological involvement in Werner's syndrome: clinical and biopsy study of a familial case.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
A Malandrini
Publications and source records attributed to A Malandrini.
Autonomic nervous system and smooth muscle cell involvement in systemic sclerosis: ultrastructural study of 3 cases.
OBJECTIVE: To investigate morphological abnormalities in nerve and smooth muscle structures of the anorectal wall underlying gastrointestinal dysfunction in patients with systemic sclerosis (SSc). METHODS: We performed deep rectal biopsy in 3 patients with limited scleroderma of relatively recent onset and intestinal symptoms. RESULTS: We found ultrastructural signs of axonal degeneration and cytoskeletal abnormalities in the bundles of unmyelinated fibers. There was also focal degeneration of smooth muscle cells, often in association with the presence of partially degranulated mast cells. Many mast cells were also observed in close relation to nerve fibers and vessels. The enteric vessels often showed basal lamina reduplication and hypertrophied endothelial cells with obliterated lumen. No significant fibrosis was found. CONCLUSION: Our findings indicate early involvement of the autonomic nervous system and to a lesser extent of smooth muscle cells. We confirmed the presence of early vascular lesions and involvement of mast cells in the pathological process.
Adult↗
Acute inflammatory neuropathy in Charcot-Marie-Tooth disease.
The authors report an association between acute inflammatory neuropathy and previously undiagnosed Charcot-Marie-Tooth 1A disease in a 15-year-old girl. Sural nerve biopsy study showed hypertrophic neuropathy with endoneurial infiltrates of macrophages and lymphocytes. This association may be coincidental, but a particular susceptibility to damage of these peripheral nerves cannot be excluded. This report confirms the importance of pes cavus as a sign of long-standing sensorimotor neuropathy.
Action Potentials↗
Identification and characterization of a highly conserved protein absent in the Alport syndrome (A), mental retardation (M), midface hypoplasia (M), and elliptocytosis (E) contiguous gene deletion syndrome (AMME).
We recently described a novel contiguous gene deletion syndrome (AMME) in Xq22.3 that includes Alport syndrome (A), mental retardation (M), midface hypoplasia (M), and elliptocytosis (E). While the Alport syndrome is due to deletion of the COL4A5 gene, no other genes are known in the region with the exception of our recent finding of the FACL4 gene. In our effort to isolate additional genes from the deleted region, we have identified the gene named AMMECR1 (Alport syndrome, mental retardation, midface hypoplasia, and elliptocytosis chromosomal region gene 1). RACE experiments and screening of cDNA libraries enabled us to obtain the entire ORF of the gene (1002 bp) followed by about 2 kb of 3'UTR. AMMECR1 is composed of six exons, shows a ubiquitous 6.5-kb transcript, and codes for a protein with a molecular mass of 35.5 kDa. Sequence analysis revealed that this gene is conserved in several species ranging from Caenorhabditis elegans and yeast to micro-organisms. Exon 2 of AMMECR1 encodes a domain consisting of six amino acids identically conserved throughout the course of evolution and whose function is as yet unknown. Analysis of the predicted protein product using ExPAsy tools raises the possibility that the gene may code for a regulatory factor potentially involved in the development of AMME contiguous gene deletion syndrome.
Amino Acid Sequence↗
Mitochondrial myopathy mimicking fibromyalgia syndrome.
Explore the source record for details and available documents.
DNA, Mitochondrial↗
Inheritance of a 38-kb fragment in apparently sporadic facioscapulohumeral muscular dystrophy.
Facioscapulohumeral dystrophy (FSHD) is an autosomal-dominant muscular disorder associated with a short (<35 kb) EcoRI/BlnI fragment resulting from deletion of an integral number of units of a 3.3-kb repeat located at 4q35. In this study, we determined fragment sizes separated by pulsed-field gel electrophoresis in a patient with an apparently sporadic case of FSHD and in his healthy family members. A 38-kb fragment was detected in the proband, in his older brother, and in their father. This finding prompted a clinical reevaluation of the father and brother. A subclinical phenotype restricted to abdominal muscle weakness was detected, and serum creatine kinase values were found to be elevated in both. The proband's brother also showed evidence of an independently occurring subtelomeric rearrangement of 4q35, which normally occurs in about 20% of the population. The identification of a "borderline" 38-kb EcoRI/BlnI fragment in an affected subject and his very mildly affected relatives extends the size range of disease alleles and expands existing data on the variable intrafamilial expressivity of FSHD. This study highlights the importance of a careful molecular and clinical analysis extended to family members of apparently sporadic cases with larger EcoRI/BlnI fragments for accurate diagnosis and appropriate genetic counseling in FSHD.
Adult↗
Ataxin 1 and ataxin 3 in neuronal intranuclear inclusion disease.
Neuronal intranuclear inclusion disease (NIID) is a multisystem neurodegenerative disorder characterized by large intranuclear aggregates in neurons of the central and peripheral nervous system. These ubiquitinated intranuclear inclusions are morphologically similar to the intraneuronal aggregates that have been identified in the CAG/polyglutamine expansion diseases. As rare aggregates in NIID contain a polyglutamine epitope, we further investigated the relationship between this disease and the CAG/polyglutamine expansion diseases. Here, we show that ataxin 1 and ataxin 3 proteins are recruited into aggregates in NIID in the absence of a CAG expansion in the SCA1 and SCA3 genes. These data support an association of NIID with the polyglutamine disorders and provide evidence of in vivo recruitment of proteins with polyglutamine tracts into intraneuronal aggregates.
Adult↗
Detection of beta-A4 amyloid and its precursor protein in the muscle of a patient with juvenile neuronal ceroid lipofuscinosis (Spielmeyer-Vogt-Sjögren).
Muscle biopsy tissue from a patient affected by the juvenile form of neuronal ceroid lipofuscinosis (NCL) was studied immunohistochemically using antibodies to beta-amyloid peptide and amyloid precursor protein. Positive reaction in muscle was specifically localized to autophagic vacuoles and blood vessel walls. Increased acid phosphatase reaction suggested enhanced lysosomal activity. We hypothesize that beta-amyloid is deposited in NCL muscle by a lysosomal mechanism similar to that proposed in other disorders involving beta-amyloid.
Adult↗
Decreased expression of laminin beta 1 in chromosome 21-linked Bethlem myopathy.
Muscle biopsies of four patients affected by chromosome 21-linked Bethlem myopathy were investigated by means of immunohistochemistry, with monoclonal antibodies for laminin chains, dystrophin and dystrophin associated glycoproteins. The objective of this study was to determine whether an altered molecular structure of collagen type VI, characteristic of Bethlem myopathy, could influence the expression of the protein complex linking the extracellular matrix with the subsarcolemmal cytoskeleton. Normal expression of all proteins was found except for laminin beta 1, along with an age related progressive deficiency of this protein in the muscle fibre basal lamina. This study shows that Bethlem myopathy linked to chromosome 21 is associated with a secondary decrease in laminin beta 1 expression.
Adolescent↗
Giant axonal neuropathy with subclinical involvement of the central nervous system: case report.
The case of a 17-year-old girl with slowly progressive sensory-motor neuropathy is described. Sural nerve biopsy showed abnormally enlarged exons filled with neurofilaments. Neurofilament accumulation was limited to the axons and was not found in other cells of the skin or peripheral nerve. The patient showed EEG and brain MRI abnormalities, but there was no clinical evidence of central nervous system involvement. Although these findings suggest an atypical attenuated form of giant axonal neuropathy, a new nosological entity cannot be excluded.
Adolescent↗
Juvenile Leigh syndrome with protracted course presenting as chronic sensory motor neuropathy, ataxia, deafness and retinitis pigmentosa: a clinicopathological report.
We herein describe a male patient who died at 37 years of age, after having suffered from a slowly progressive syndrome of chronic sensory motor neuropathy, deafness, retinitis pigmentosa and ataxia. The neuropathological study showed symmetric areas of necrosis and demyelination affecting the cerebellum and brainstem. The type of lesion was consistent with the characteristics of Leigh Syndrome. On the basis of the histology of the lesions, we believe that they appeared only a few months before the death of the patient. We underline the atypical clinical picture and suggest that, in certain cases, brain MRI may not be a reliable diagnostic tool.
Adult↗
Schnyder corneal crystalline dystrophy: description of a new family with evidence of abnormal lipid storage in skin fibroblasts.
Schnyder corneal crystalline dystrophy (SCCD) comprises corneal opacities often associated with precocious arcus senilis and genua valga. The metabolic defect seems to be related to abnormal lipid storage in the central part of the cornea, especially the anterior stroma, consisting mainly of nonesterified cholesterol. Plasma lipid levels are not always increased suggesting that the disease may be due to abnormal lipid metabolism limited to the cornea. We observed a family with typical SCCD, in 1 case associated with mental retardation and mild cerebellar hypoplasia. Results of serum lipid analysis of all patients were normal. Ultrastructural study of a skin biopsy specimen and fibroblast pellet showed membrane-bound spherical vacuoles containing lipid material. Cultured fibroblasts stained by filipin, a fluorescent probe that specifically binds unesterified cholesterol, showed abnormal cytoplasmic fluorescent material, suggesting abnormal cholesterol metabolism. The presence of neurological impairment, associated with SCCD in 1 of our cases, may be regarded as coincidental. Evidence of storage lipids in skin and cultured fibroblasts suggests that the disorder of intracellular cholesterol metabolism is not limited to the cornea and that skin biopsy may be a useful method to confirm the diagnosis.
Adult↗
Immunofluorescence study of a muscle biopsy from a 1-year-old patient with Walker-Warburg syndrome.
A previous study of two patients with Walker-Warburg syndrome (WWS) showed a severe deficiency of the extracellular matrix protein laminin beta2 chain and alpha-sarcoglycan (adhalin) in skeletal muscle fibers. More recently, however, other researchers have shown that in their WWS patients the expression of the laminin beta2 chain and alpha-sarcoglycan was normal. Here we describe a 1-year-old boy affected with WWS. We performed immunohistochemical studies on a muscle biopsy from this patient using monoclonal antibodies against dystrophin, dystrophin-associated glycoproteins and several proteins of the extracellular matrix. We confirm previously reports as far as the diminished expression of laminin beta2 chain and alpha-sarcoglycan is concerned. The expression of some other laminins was unusual, whereas the expression of collagen IV and VI was normal. These results suggest that complex syndromes like WWS are quite heterogeneous, although they might represent variant expressions of a single pathological entity.
Biopsy↗
Neuronal intranuclear inclusion disease: neuropathologic study of a case.
We report neuropathological findings in a 22-year-old man affected with neuronal intranuclear inclusion disease. The inclusions affected to different extents the various structures of the central nervous system, being more numerous in cerebral cortex, inferior olives, hypoglossal and oculomotor nuclei. They ultrastructurally differed from Marinesco bodies. In the neurons of the substantia nigra, we occasionally observed intranuclear inclusions resembling the so-called rodlets of Roncoroni. We did not observe inclusions in the extraneuronal tissues. There was no apparent correlation between frequency of the inclusions and neuronal loss. Intranuclear inclusions were found in many morphologically normal neurons. We suggest that the intranuclear inclusions are the marker of a distinctive disorder, even though their role in neuronal degeneration remains to be clarified.
Adult↗
Ultrastructural study of enteric ganglia in three patients with Rett syndrome.
In order to verify whether a pseudo-obstruction syndrome was associated with morphological changes in enteric ganglia, we performed an ultrastructural study on rectal biopsy specimens in three patients with Rett syndrome. Features of enteric neurons, detected to a different extent in all three biopsy specimens, included an abnormal dilatation of endoplasmic reticulum with a disorganization of cisternae of the Golgi apparatus, and masses of unidentified electron-dense granulo-filamentous material, probably of lipidic origin, observed in the perikaryon. Large electron-lucent membrane-bound vacuoles were found mostly within satellite glial cells. Sometimes, the axon terminals were swollen and showed intraxonal vacuolization. We conclude that the reported findings do not represent a specific sign of degeneration and do not constitute a significant morphological marker of disease.
Child↗
Hereditary motor and sensory neuropathy Lom type in an Italian Gypsy family.
We describe a form of hereditary motor and sensory neuropathy (HMSN) affecting four siblings in an Italian family of Gypsy ethnic origin with both clinical and pathological findings very reminiscent of the HMSN Lom type (HMSNL), recently described in a group of Bulgarian Gypsies. Genetic analysis demonstrated linkage to chromosome 8q24 and conserved haplotypes in the HMSNL region, thus confirming that this is the first Gypsy family outside the Balkans suffering from the same disorder.
Adolescent↗
Charcot-Marie-Tooth disease: an intermediate form.
Explore the source record for details and available documents.
Adult↗
CAG repeat expansion in an italian family with spinocerebellar ataxia type 2 (SCA2): a clinical and genetic study.
We report an Italian family in which molecular genetic analysis showed expansion of CAG repeats indicative of the SCA2 genotype. This family confirms that ataxia, ophthalmoparesis and sensory peripheral neuropathy are the salient features of the SCA2 phenotype. In the present cases, early onset and mental deterioration were important additional findings. Nerve biopsy findings were compatible with a chronic axonopathy. We found a direct correlation between length of triplet expansion and severity of the clinical symptoms. Of particular interest is the late-onset phenotypical expression in a patient with 34 repeats.
Adult↗