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F Chapon

Publications and source records attributed to F Chapon.

At least 37 records · Page 2Linked to original sources
PubMed1999

A second locus for autosomal dominant myopathy with proximal muscle weakness and early respiratory muscle involvement: a likely chromosomal locus on 2q21.

We recently mapped a locus for a new variant of autosomal dominant myopathy (Swedish families) with proximal muscle weakness, early respiratory muscle involvement, and unique muscle biopsy findings to chromosomal region 2q24-31. In this study, a French family with a similar clinical phenotype and pathology (muscle biopsy) was investigated to see whether the disease gene associated with the myopathy is mapped to the same region as the one in the Swedish families; however, chromosomal region 2q24-q31 was completely excluded. In order to localise the disease gene for the French family, a genome-wide scan was performed using polymorphic microsatellite markers. A maximum two-point lod score of 2.11 (the highest lod score that can be achieved in this family) was obtained for the markers in the region between D2S1272 and D2S1260, spanning 4 cM. This result suggests that the gene responsible for the French form is likely to be located on chromosome 2q21.

Chromosome Mapping↗
PubMed1999

Axonal phenotype of Charcot-Marie-Tooth disease associated with a mutation in the myelin protein zero gene.

A French family had Charcot-Marie-Tooth disease type 2 (CMT2) which was characterised by late onset of peripheral neuropathy involvement, Argyll Robertson-like pupils, dysphagia, and deafness. Electrophysiological studies and nerve biopsy defined the neuropathy as axonal type. Genetic analysis of myelin protein zero (MPZ) found a mutation in codon 124 resulting in substitution of threonine by methionine. One of the patients, presently 30 years old, showed only Argyll Robertson-like pupils as an objective sign but no clinical or electrophysiological signs of peripheral neuropathy.

Adolescent↗
PubMed1999

IgE multiple myeloma.

IgE multiple myeloma is a rare disease characterized by a high frequency of Bence-Jones proteinuria and plasma cell leukaemia when compared to other isotypes of monoclonal proteins. Only 35 cases have been reported. We describe a 70-year-old woman with a stage III IgE kappa multiple myeloma presenting with a sacral plasmacytoma. Immunological and biochemical studies showed IgE kappa producing tumoral plasma cells. Serum total IgE was high without clinical symptoms suggesting an hyperIgE syndrome or mast cell activation. The patient underwent surgical removal of the sacral tumor and monthly melphalan-prednisone treatment together with intravenous pamidronate infusions. Magnetic Resonance Imaging (MRI) of the dorsolumbar spine revealed an epidural process leading to T6-T9 radiotherapy. Bone densitometry showed a decreased bone mineral content supporting the management of myeloma-related osteoporosis with bisphosphonate infusions. A good partial response with plateau-phase and increase of bone mineral content was achieved after 1 year of treatment and still persists after a 28 months follow-up.

Aged↗
PubMed1999

[Dysembryoplastic neuroepithelial tumors. Report of 8 cases including two with unusual localization].

OBJECTIVES: Dysembryoplastic neuroepithelial tumors (DNTs) are usually located within the supratentorial cortex. We present a series of eight cases of DNTs including two cases with an extracortical location, one in the caudate nucleus, the other one expanded in the lateral ventricule, septum and fornix. An origin from secondary germinal layers, as previously suggested, can explain these extracortical locations. MATERIAL AND METHODS: Of the eight patients, seven had partial epileptic seizures and one intracranial hypertension. All patients underwent clinical examination, a computed tomographic (CT) scan, a magnetic resonance imaging (MRI) and a surgical removal of the lesion with histological examination. RESULTS: Clinical examination was normal except in the case with intracranial hypertension where a bilateral papillary oedema was found. In seven cases the CT scan showed a hypodense lesion of pseudocystic appearance. All lesions were hypointense on T1-weighted and hyperintense on T2-weighted MRI. Contrast enhancement was observed in two cases. The lesion was intracortical in six cases and extracortical in the remaining two: one in the head of the caudate nucleus and one in the trigonoseptal region. Histological examination identified an appearance of DNT with a specific glioneuronal element in six cases. CONCLUSION: The diagnosis of DNT can be suspected before histological examination on radiological features, chiefly because the tumor is located in the supratentorial cortex. However, extracortical locations do exist, even if unusual. As DNTs are always benign, knowledge and accurate diagnosis of these atypical cases are mandatory in order to avoid useless and even deleterious additional treatments, such as radiotherapy.

Adolescent↗
PubMed1998

A missense mutation in the alphaB-crystallin chaperone gene causes a desmin-related myopathy.

Desmin-related myopathies (DRM) are inherited neuromuscular disorders characterized by adult onset and delayed accumulation of aggregates of desmin, a protein belonging to the type III intermediate filament family, in the sarcoplasma of skeletal and cardiac muscles. In this paper, we have mapped the locus for DRM in a large French pedigree to a 26-cM interval in chromosome 11q21-23. This region contains the alphaB-crystallin gene (CRYAB), a candidate gene encoding a 20-kD protein that is abundant in lens and is also present in a number of non-ocular tissues, including cardiac and skeletal muscle. AlphaB-crystallin is a member of the small heat shock protein (shsp) family and possesses molecular chaperone activity. We identified an R120G missense mutation in CRYAB that co-segregates with the disease phenotype in this family. Muscle cell lines transfected with the mutant CRYAB cDNA showed intracellular aggregates that contain both desmin and alphaB-crystallin as observed in muscle fibers from DRM patients. These results are the first to identify a defect in a molecular chaperone as a cause for an inherited human muscle disorder.

Animals↗
PubMed1998

Effects of damage to the basal forebrain on brain glucose utilization: a reevaluation using positron emission tomography in baboons with extensive unilateral excitotoxic lesion.

Neuronal loss in the basal forebrain cholinergic structures and frontotemporal hypometabolism are two characteristics of Alzheimer's disease, but their interrelations still are unsettled. We previously reported that unilateral electrolytic lesions of the nucleus basalis of Meynert in baboons were associated with marked but transient cortical hypometabolism. The current study reevaluates this issue using improved methodology. Baboons with unilateral ibotenic acid lesion of all three basal forebrain cholinergic structures (IBO group) were compared with sham-operated animals. The CMRglc was measured with high-resolution coronal positron emission tomography scanning coregistered with magnetic resonance imaging, before surgery and serially between 4 and 72 days afterward. Severe histologic basal forebrain damage and a decrease of more than 50% in cortical choline acetyltransferase activity were found postmortem in the IBO group. Transient and nonspecific hypometabolism was found in the needle track area in both groups. Compared with the sham-operated group, only marginally significant decreases in ipsilateral-contralateral CMRglc ratios were observed in the IBO group, affecting only 1 of 14 neocortical areas investigated (the anterior temporal cortex) at a single postsurgical time (day 14), and the posterior hippocampal region at days 14 and 38. Furthermore, there was no consistently significant correlation between ipsilateral-contralateral CMRglc ratios and cortical choline acetyltransferase activity values in any of the four regions analyzed. These results suggest that cholinergic deafferentation play at best a marginal role in the brain hypometabolism observed in Alzheimer's disease.

Alzheimer Disease↗
PubMed1997

Pituitary apoplexy of a gonadotroph adenoma following gonadotrophin releasing hormone agonist therapy for prostatic cancer.

Treatment of prostatic cancer with GnRH agonist is a medical alternative to surgical castration, although hyperstimulation of the tumor can occur. We describe an unusual unwanted effect of such a treatment which unmasked a clinically silent gonadotroph adenoma. A 62-year-old man developed after the first injection of leuprorelin-depot a sudden intracranial hypertension, which was related to apoplexy of an unknown pituitary adenoma. Its gonadotroph origin was recognized after surgery by immunocytochemistry. Retrospectively, the tumor was shown to secrete in vivo both FSH and LH when on therapy with the agonist, demonstrating the lack of desensitization. Testosterone levels were also markedly and sustainly high when on therapy, a particularly unwanted effect in prostatic cancer. As gonadotroph adenomas occur in men in the same age group as prostatic cancer, the question is raised whether hormonal testing and pituitary imaging should be performed before starting a therapy with GnRH agonist in men.

Adenoma↗
PubMed1997

Mutations in the X-linked form of Charcot-Marie-Tooth disease in the French population.

The present study reports eight additional mutations in the connexin32 gene associated with the X-linked form of Charcot-Marie-Tooth disease. One of these mutations was found twice in two apparently unrelated families. This form of the disease is demyelinating and dominant. However, patient selection for mutational screening should not be limited to these criteria since presentation can either be familial or sporadic, and some patients may be incorrectly classified as suffering from an 'axonal' form. These new mutations complete our previously published work on 12 other mutations and enable meaningful observation in a representative sample of the French population. Mutations are found in all regions of the gene. The most frequently observed mutations were those affecting arginines and mainly involved CpG sequences. Compared with other sources, some of the mutations were present at a higher frequency in the French population.

Adolescent↗
PubMed1997

Proliferating cell nuclear antigen (PCNA) in cerebral cavernomas: an immunocytochemical study of 42 cases.

BACKGROUND: The natural history and growth mechanisms of cerebral cavernous angiomas are unclear, which makes them difficult to manage. We attempted to evaluate the evolutive potential of cavernomas by studying the proliferative capacity of cells. METHODS: We studied 42 histologically verified cavernomas with monoclonal antibody to proliferating cell nuclear antigen (PCNA), an accessory protein of the cell cycle, the rate of which is increased in proliferative cells. The PCNA Labeling Index (PCNA LI) was calculated in each case, and the results were compared with histologic findings (lacy areas, thick walls, thrombi, hemosiderin) and clinical features (epilepsy, hematomas, pseudotumorous signs). RESULTS: Thirty-six of 42 cases (85.7%) revealed stained cells. PCNA LI ranged from 1 to 48% (mean: 23.39%). Statistical analyses showed a positive correlation between PCNA LI and the extent of lacy areas (p < 0.05). On the contrary, collagenous-walled and thrombotic areas rarely showed positively stained cells. We found no relationship between PCNA LI and clinical features. CONCLUSIONS: A proliferative capacity of endothelial cells does exist in some areas of cavernomas and may explain, besides thromboses and hemhorrages, the growth and even de novo appearance of these lesions. Occurrence of fragile blood cavities, thickening of others, and changes in blood flow may influence the evolution of lesions. Our results suggest that in cavernomas, some areas may undergo specific changes, which makes them more dynamic lesions than previously thought.

Adolescent↗
PubMed1997

The in vivo metabolic pattern of low-grade brain gliomas: a positron emission tomographic study using 18F-fluorodeoxyglucose and 11C-L-methylmethionine.

OBJECTIVE: The object of the present study was to identify metabolic differences between low-grade astrocytomas and oligodendrogliomas and to improve their diagnosis and noninvasive assessment, because both types of tumors look very similar from the point of view of clinical and radiological data (as assessed by computed tomography and magnetic resonance imaging). METHODS: Before any aggressive treatment, 22 patients with primary low-grade gliomas (astrocytomas in 12 patients and oligodendrogliomas in 10) were investigated with positron emission tomography for both glucose metabolism (18F-fluorodeoxyglucose) and amino acid uptake (11C-L-methylmethionine). An original software that allows a full metabolic analysis of the tumor region of interest (defined from the T1-weighted magnetic resonance image) and compares tumor tissue uptake tracer concentrations with average healthy tissue values has been implemented for data processing. Heterogeneity of each individual tumor has been taken into account and was expressed in histograms, which provided data about the mean and also extreme and intermediate values of tracer concentrations and the way these values are distributed among the full tumor mass. RESULTS: It has been shown that both tumor types exhibit a glucose hypometabolism (slightly more pronounced with astrocytomas), whereas they strongly differ in methionine uptake, which is high in all oligodendrogliomas and either decreased, normal, or moderately increased in astrocytomas. This latter metabolic difference between both tumor populations may be partially explained by their different cell densities. CONCLUSION: This study suggests that despite similar radiological and clinical presentations, these two kinds of low-grade gliomas are metabolically different and could therefore have specific responses to different therapies. Moreover, their in vivo metabolic follow-up with positron emission tomography should rely on different parameters, depending on their histological type; methionine uptake may be more relevant than glucose metabolism in the follow-up of oligodendrogliomas.

Adult↗
PubMed1997

Familial cavernous malformations in a large French kindred: mapping of the gene to the CCM1 locus on chromosome 7q.

OBJECTIVES: To characterise clinically a large French family affected with cerebral cavernomas and to check for linkage of this condition to chromosome 7. METHODS: A family, originating from Normandy and in which five members had undergone surgery for cavernomas, was extended. All members older than 18 were studied clinically and by neuroimaging. Genetic linkage analysis was conducted using 11 polymorphic microsatellite markers located between D7S502 and D7S479. RESULTS: The family included three generations. Among the 25 members investigated, 11 had an abnormal cerebral MRI, eight of them being symptomatic, and 12 were asymptomatic with a normal MRI. The status of the two remaining members could not be established on the basis of clinical and MRI data. The family reported shares some striking features with other previously linked families--namely, a high clinical penetrance and the presence of multiple lesions within most of the affected members. A lod score of 4.04 was obtained with marker D7S657 with no recombinant. Significant lod scores were also obtained with D7S524 (Zmax=3.32 at 0=0.00) and D7S630 (Zmax=3.44 at 0=0.00). These results establish linkage of the condition found in this family to chromosome 7. Haplotype analysis strongly suggests that the gene is telomeric to D7S802 and centromeric to D7S479. CONCLUSIONS: These data confirm linkage of cerebral cavernous malformations to chromosome 7 in a non-Hispanic family.

Adolescent↗
PubMed1997

New mutations in the X-linked form of Charcot-Marie-Tooth disease.

Mutations in the gene for connexin 32 are associated with a chromosome X-linked form of Charcot-Marie-Tooth disease. The prevalence of this form is probably underestimated. We screened 12 candidate families and found 7 missense mutations of which 4 are new. These mutations are located in intra- and extramembraneous parts of the protein. Some mutations are probably present with a higher frequency. This study further confirms variation of connexin 32 mutations with scarcity in the second transmembrane domain and, so far, absence in the fourth transmembrane domain and in the carboxy-terminal region.

Charcot-Marie-Tooth Disease↗
PubMed1996

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, genetic homogeneity, and mapping of the locus within a 2-cM interval.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a recently identified autosomal dominant cerebral arteriopathy characterized by the recurrence of subcortical infarcts leading to dementia. A genetic linkage analysis conducted in two large families recently allowed us to map the affected gene on chromosome 19 in a 12-cM interval bracketed by D19S221 and D19S215. In the present study, these first 2 families and 13 additional ones, including a total of 199 potentially informative meiosis, have been genotyped with eight polymorphic markers located between D19S221 and D19S215. All families were linked to chromosome 19. The highest combined lod score (Zmax = 37.24 at theta = .01) was obtained with marker D19S841, a new CAn microsatellite marker that we isolated from chromosome 19 cosmids. The recombinant events observed within these families were used to refine the genetic mapping of CADASIL within a 2-cM interval that is now bracketed by D19S226 and D19S199 on 19p13.1. These data strongly suggest the genetic homogeneity of this recently identified condition and establish the value of its clinical and neuroimaging diagnostic criteria. Besides their importance for the ongoing positional cloning of the CADASIL gene, these data help to refine the genetic mapping of CADASIL relative to familial hemiplegic migraine and hereditary paroxysmal cerebellar ataxia, conditions that we both mapped within the same chromosome 19 region.

Cerebral Arterial Diseases↗
PubMed1996

Molecular diagnosis of Charcot-Marie-Tooth 1A disease and hereditary neuropathy with liability to pressure palsies by quantifying CMT1A-REP sequences: consequences of recombinations at variant sites on chromosomes 17p11.2-12.

The most frequent form of Charcot-Marie-Tooth disease (CMT1A; OMIM118.220) is the result of a duplication on chromosome 17 in pll.2-p12. This region contains PMP22, a gene expressed in peripheral myelin. The mutation results from an unequal crossing-over involving repeated sequences, CMT1A-REP, located on both sides of the duplicated region. The reciprocal product of this recombination is a deletion of the same region, which is associated with hereditary neuropathy with liability to pressure palsies (HNPP; OMIM162.500). Proximal and distal CMT1A-REP sequences can be distinguished by the presence of a variant EcoRI site. We quantified the number of these repeat sequences in 36 CMT1A and 40 HNPP patients. CMT1A-REP sequences are involved in almost all of the mutations. The majority of recombination breakpoints occur distally from the variant EcoRI site. However, a few have a breakpoint proximal to this site, which creates the risk of misinterpretation with respect to a duplicated/deleted status.

Charcot-Marie-Tooth Disease↗
PubMed1996

[Akinetic mutism with right hemiplegia caused by infarction in the territory of the left anterior cerebral artery].

A 65 years old woman with chronic high blood pressure and diabetes mellitus presented with a mutism akinetic of sudden onset and a right total hemiplegia with a Babinski sign secondary to a left anterior cerebral artery infarction. She had had six months earlier a transient gait disturbance. At that time, the CT scan showed lacunar infarcts of the head of both caudate nuclei. Neuropathological examination revealed that the left infarction of the anterior cerebral artery involved the superior frontal gyrus, the supplementary motor area, the cingulate gyrus and the corpus callosum. There were also multiple lacunes of the head of both caudate nuclei, anterior limb of the internal capsules, white matter, basal ganglia and thalami. The mutism akinetic was thought to be the result of a bilateral disruption of a functional loop including on each side, the supplementary motor area, the cingulate gyrus, the subcallosal tract and the head of the caudate nucleus. On the right side, the lesion of the caudate nucleus could have interrupted this loop normally involved in the induction of voluntary movements and in the communication with the external surroundings.

Aged↗