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G Chazot

Publications and source records attributed to G Chazot.

At least 19 recordsLinked to original sources
PubMed2001

Polymorphic short tandem repeats for diagnosis of the Charcot-Marie-Tooth 1A duplication.

BACKGROUND: A 1.5-Mb microduplication containing the gene for peripheral myelin protein 22 (PMP22) on chromosome 17p11.2-12 is responsible for 75% of cases of the demyelinating form of Charcot-Marie-Tooth disease (CMT1A). Methods for molecular diagnosis of CMT1A use Southern blot and/or amplification by PCR of polymorphic poly(AC) repeats (microsatellites) located within the duplicated region, or the detection of junction fragments specific for the duplication. Difficulties with both strategies have led us to develop a new diagnostic strategy with highly polymorphic short tandem repeats (STRs) located inside the CMT1A duplicated region. METHODS: We tested 10 STRs located within the duplication for polymorphic behavior. Three STRs were selected and used to test a set of 130 unrelated CMT1A patients and were compared with nonduplicated controls. The study was then extended to a larger population of patients. Alleles of interest were sequenced. A manual protocol using polyacrylamide electrophoresis and silver staining and an automated capillary electrophoresis protocol to separate fluorescently labeled alleles were validated. RESULTS: We identified three new STRs covering 0.55 Mb in the center of the CMT1A duplication. One marker, 4A, is located inside the PMP22 gene. The two others, 9A and 9B, more telomerically positioned, have the highest observed heterozygosity reported to date for CMT1A markers: 0.80 for 9A, and 0.79 for 9B. Tetra- and pentanucleotide repeats offered clear amplification, accurate sizing, and easy quantification of intensities. CONCLUSIONS: Combined use of the three STRs allows robust diagnosis with almost complete informativeness. In our routine diagnosis for CMT1A, they have replaced the use of other polymorphic markers, either in a manual adaptation or combined with fluorescence labeling and allele sizing on a DNA sequencer.

Charcot-Marie-Tooth Disease↗
PubMed2000

Clinical report of three patients with hereditary hemochromatosis and movement disorders.

Neurologic manifestations are rarely described in hereditary hemochromatosis (HH). We describe three patients with HH and movement disorders. Patient 1, a 69-year-old man, had a 13-year history of disabling cerebellar syndrome, action tremor and myoclonus, and secondary dementia. Patient 2 was a 40-year-old man with a 9-year history of cerebellar syndrome, head and arm tremor, and cervical dystonia. Patient 3, a 75-year-old woman, had a 5-year history of rapidly disabling parkinsonian syndrome unresponsive to levodopa. The diagnosis of HH was established in the three patients by iron tests, evidence of a C282Y mutation, and, in two patients, by liver biopsy. High-field T2-weighted magnetic resonance imaging showed hyperintense signals in hemispheric white matter in patient 1, cerebellar atrophy in patient 2, and cerebellar and cerebral atrophy in patient 3 and no significant hypointense signals in the three patients. Phlebotomies and symptomatic treatments did not change the course of the disease. Our cases are compared with the five previously reported observations of HH with movement disorders. This rare association is one cause of the chronic acquired non-Wilsonian hepatocerebral degeneration syndromes and represents a separate entity from aceruloplasminemia. The pathophysiologic mechanism of movement disorders in HH is unresolved. No hepatic insufficiency and portosystemic encephalopathy is evidenced in our cases, whereas the putative role of abnormal iron load remains to be ascertained. HH should be investigated more systematically in patients with movement disorders.

Adult↗
PubMed2000

The first case of new variant Creutzfeldt-Jakob disease in France: clinical data and neuropathological findings.

Clinical data and autopsy findings in a case of new variant Creutzfeldt-Jakob disease (vCJD) are reported. This case, the first histologically confirmed case described outside the United Kingdom, very much resembles the cases described by Will et al. [(1996) Lancet 347:921-925] and Zeidler et al. [(1997) Lancet 350:903-908, 908-910]. Neuropathological studies failed to reveal any conspicuous clues that could be relevant for understanding the pathophysiology of the disease. For epidemiological surveillance, neuropathologists should scrutinize suspected cases keeping in mind the possibility of vCJD.

Adult↗
PubMed2000

[Amyotrophic lateral sclerosis: a role for enteroviruses?].

Amyotrophic lateral sclerosis (ALS) is the most frequent motor neuron disease. Although it is a clinically well defined disease, its etiology remains unknown. Among, various hypotheses, the putative role of enteroviruses has been recently suggested by the detection of enteroviral sequences in neurons of spinal cord samples from ALS patients. However, there is a lack of consensus on the role of EV in ALS. In the present paper, we summerized the pathogenic role of these viruses, analyzed the discrepancy between different studies and speculated on the possible role of enteroviruses in ALS.

Amyotrophic Lateral Sclerosis↗
PubMed2000

[Non-familial Creutzfeldt-Jakob disease: a study of 53 cases].

Creutzfeldt-Jakob disease (CJD) is the most frequent human spongiform encephalopathy. We have analyzed 53 cases of definite non familial CJD over a study period of 28 years. All were autopsied in the same neuropathological unit. Clinical and epidemiological data were in accordance with previous studies: low incidence of CJD under the age of 40, high incidence around the sixty years of age (26%) a sex ratio at 0.65 and high frequency of myoclonus, dementia and cerebellar ataxia during evolution (78%). This study highlights the rapidity at the onset of the disease (within 24 hours) in 16% of the cases. EEG disclosed typical pseudoperiodic activity in only 53% of cases and cerebral MRI showed high T2 signal intensity in basal nuclei in 15%. This regional study is the second of its nature to be carried out in France, the first one covering the area of Paris.

Adult↗
PubMed1999

CTG instability in myotonic dystrophy: molecular genetic analysis of families from south-eastern France with characteristics of intergenerational variation in CGT repeat numbers.

We report clinical, genetical and genealogical findings in 149 French families from the Rhône-Alpes area studied over a 5-year period. There was a significant excess of DM females compared to DM males with (CTG) repeat sizes between 1-2 kb. The mean maternal (CTG) repeat size was higher than paternal repeat size. Anticipation phenomenom was significantly higher after maternal than after paternal transmission. A significant correlation between parental (CTG) repeat size and intergenerational variation both in paternal and maternal transmissions was observed. The anticipation phenomenom was more important for sons than daughters particularly after maternal transmission. The mean (CTG) repeat size in mothers of CDM cases was about twice that of mothers of NCDM children. The risk of giving birth to a CDM child increased considerably when the number of maternal (CTG) repeats was over 300 (CTG). A significant excess of DM females was observed. They had on average 24% fewer children than male patients. Paternal transmission (63.6%) of DM occurred more frequently than maternal transmission (52.7%).

Female↗
PubMed1998

A de novo missense mutation (R1623Q) of the SCN5A gene in a Japanese girl with sporadic long QT sydrome. Mutations in brief no. 140. Online.

Two missense mutations and a nine-nucleotide deletion of the cardiac sodium channel (SCN5A) gene have been shown to cause long QT syndrome (LQTS) in several familial cases. We identified a novel missense mutation (R1623Q) of the SCN5A gene in a Japanese girl with sporadic LQTS. We used polymerase chain reaction, single-strand conformation polymorphism analysis and DNA sequence analysis to identify a mutation of the SCN5A gene in the patient. A single nucleotide substitution of guanine to adenine, in codon 1612, changed the coding sense of the SCN5A from arginine to glutamine (R1623Q) in the S4 segment of domain IV which is a highly conserved region of the SCN5A. This mutation was not identified in the unaffected biological parents and brother of the patient, and 100 normal, unrelated individuals. This finding is the first evidence of a de nova mutation in SCN5A associated with LQTS.

Amino Acid Substitution↗
PubMed1998

Course of valvular strands in patients with stroke: cooperative study with transesophageal echocardiography.

BACKGROUND: Native valve strands might be related to the acute stage of thrombosis or might suggest a long-term valvular change. We aimed to estimate changes in the strands in patients with stroke through a serial transesophageal echocardiographic (TEE) study. METHODS AND RESULTS: A study was conducted among patients who were referred for TEE for stroke or cardiac pathology. Patients had TEE examinations with a 5-MHz multiplane TEE probe. Echocardiography was repeated 3 months later in patients with stroke. TEE was performed in 180 patients admitted to cardiology units and in 160 patients referred to neurology units. Among 34 patients with valvular strands, 30 were referred to neurology for stroke, whereas 4 patients were admitted to cardiology (18.8% versus 2.2%, difference 16.5%, 95% confidence interval 10% to 22.9%, P =.001). Strands were located on the mitral valve in 16 patients, the aortic valve in 6 patients, and both left heart valves in 8 patients. Among the 38 valves with strands, 17 (44. 7%) were morphologically normal, 4 (10.5%) were thickened, 7 (18.4%) were redundant, and 10 (26.3%) had both abnormalities. TEE showed other abnormalities in 16 (53.3%) patients, whereas 14 patients had only strands. Twenty-six (86.6%) patients had a second TEE study 3 months later. Strands were not found in 4 (15.4%) patients (95% confidence interval 4.3% to 34.9%). CONCLUSIONS: Valvular thickening or redundancy may predispose valves to strand formation. Native valve strands usually persist and thus reflect a chronic valvular change.

Adolescent↗
PubMed1998

The physiology and pharmacology of melatonin in humans.

Melatonin (MLT) is a methoxyindole secreted principally by the pineal gland. It is synthesized at night under normal environmental conditions. The endogenous rhythm of secretion is generated by the suprachiasmatic nuclei and entrained by the light/dark cycle. Light is able to both suppress or entrain MLT production on light schedule. The nyctohemeral rhythm of this hormone can be determined by repeated measurement of plasma or saliva MLT or urine sulfatoxy-MLT, the main hepatic metabolite. MLT can be considered as the output (the hand) of the endogenous clock. Since the regulating system follows a central and sympathetic nervous pathway, an abnormality at any level could unspecifically modify the MLT secretion, especially in patients with sympathalgia or dysautonomia. MLT plays the role of an endogenous zeitgeber on core temperature or sleep-wake cycle. Exogenous MLT is able to influence the endogenous secretion of the hormone according to a phase-response curve. There are practical implications for this property in situations when biological rhythms are disturbed (jet-lag syndrome, delayed sleep phase syndrome, insomnia in blind people, shift-work, insomnia in elderly people). Improvement of pharmaceutical forms (controlled release preparations) or development of MLT analogs could lead to decisive progress.

Adenylyl Cyclases↗
PubMed1997

Giant lambl excrescences. An unusual source of cerebral embolism.

BACKGROUND: A possible association of giant Lambl excrescences (LEs) with stroke has been suggested. However, the treatment of giant LEs is controversial because minimal data are available. OBJECTIVE: To clarify the management of giant LEs through a clinicopathologic study. CASE SERIES: Three young patients (2 women and 1 man) who experienced ischemic stroke were studied. Results of general examinations were normal, as were chest x-ray films, electrocardiograms, ultrasonograms of the neck, and cerebral angiograms. Extensive serological and blood testing failed to show any coagulopathies or systemic disorders that favored a stroke in these patients. Transesophageal echocardiography showed a mitral valve lesion (width, > 1 mm). Two patients (cases 1 and 3) were discharged on a regimen of anticoagulant therapy and sequential transesophageal echocardiographic monitoring was planned, whereas 1 patient (case 2) was promptly scheduled for surgery. A second stroke occurred in patients 1 and 3 at 3 and 6 months, respectively, thus leading to surgery in these 2 patients. Findings from histopathologic studies were consistent with the diagnosis of giant LEs. The patients' outcomes were uneventful after surgery, and none had a recurrence of a stroke. CONCLUSIONS: A relationship between giant LEs and stroke may be suggested. In patients who have transesophageal echocardiographic findings that are consistent with this diagnosis and recurrent stroke despite antithrombotic therapy and without an alternative explanation for the ischemic symptoms, surgery should be considered in view of these findings.

Adult↗
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

Nocturnal plasma melatonin profile and melatonin kinetics during infusion in status migrainosus.

The plasma melatonin profile was significantly disturbed (phase-shift of the maximum melatonin level) in four out of six female sufferers from status migrainosus, compared with nine healthy controls. The number of secretion peaks was similar in both groups. A nocturnal 20 micrograms melatonin infusion (from 21.00 to 01.00 h) evoked plasma melatonin levels slightly higher than a physiological secretion peak. During infusion, the episodes of secretion were reinforced and the endogenous plasma profile was phase-advanced in two patients displaying a phase-delay. These data suggest impaired pineal function in migraine. In the absence of side effects of melatonin infusion, the relief of certain migraine symptoms described by our patients might support a controlled trial of melatonin in migraine.

Adult↗
PubMed1997

Clinical and electrophysiological phenotype of a homozygously duplicated Charcot-Marie-Tooth (type 1A) disease.

Type 1A of Charcot-Marie-Tooth disease (CMT1A) is associated with a microduplication of chromosome 17 (region 17p11.2) which contains PMP22, an important gene for peripheral nerve myelination. Patients carrying two duplications are expected to have a more severe phenotype, close to the Dejerine-Sottas syndrome. In this article, we report a family of 5 CMT1A patients in whom the unrelated father and mother carry a 17p11.2 duplication. The 2 daughters carry only one duplication (one given by the father, the other given by the mother), but the son carries two 17p11.2 duplications. Interestingly, the clinical phenotype of the son is more severe (scoliosis) compared to those of his sisters, but his motor nerve conduction velocities are in the range of a heterozygote CMT1A patient. The mechanisms leading to a more severe phenotype for CMT1A are discussed and may not be strictly related to lower nerve conduction velocities.

Adult↗
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↗