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Biomedical subjects

A Ducros

Publications and source records attributed to A Ducros.

30 records · Page 2Linked to original sources
PubMed1997

Mapping of a second locus for familial hemiplegic migraine to 1q21-q23 and evidence of further heterogeneity.

Familial hemiplegic migraine (FHM) is an autosomal dominant variety of migraine with aura. We previously mapped an FHM gene on the short arm of chromosome 19. Mutations in this gene, recently shown to be the alpha1 subunit of a P/Q-type voltage-dependent calcium channel, CACNL1A4, are involved in approximately 50% of unselected FHM families and in all families where migraine attacks are associated with permanent cerebellar ataxia. As a first step toward the identification of other FHM genes, we conducted a genetic linkage analysis in one large French pedigree and showed significant linkage to two microsatellite markers D1S2635 (Zmax: 3.33 at theta = 0.05) and D1S2705 (Zmax: 3.64 at theta = 0.05), establishing the existence of a second locus for FHM (FHM2) on chromosome 1q21-q23. Analysis of six additional FHM families favored linkage to this locus in two of them; linkage was excluded in the last four families, indicating further heterogeneity. Chromosome 1-linked families differ from the ones linked to chromosome 19, because penetrance in those families is much lower, and in some of their members, epileptic seizures occur during severe migraine attacks.

Chromosome Mapping↗
PubMed1996

A human homolog of bacterial acetolactate synthase genes maps within the CADASIL critical region.

CADASIL, a recently identified autosomal dominant condition characterized by the recurrence of subcortical infarcts leading to dementia, was previously mapped to chromosome 19p13.1 within a 2-cM interval, D19S226-D19S199. No recombination event was observed with D19S841, a highly polymorphic microsatellite marker isolated from a cosmid mapped to this region. We recently identified within this cosmid a conserved sequence that we used to screen a fetal brain cDNA library and isolated an ubiquitous and abundantly transcribed gene. We did not detect any mutation of this gene in CADASIL patients, suggesting that it is not implicated in this disorder. Interestingly, this gene encodes a putative protein homologous to several thiamine pyrophosphate-binding proteins previously identified in bacteria, yeast, and plants. The proteins with the highest degree of similarity were the acetolactate synthase enzymes which, in prokaryotes, are involved in the branched chain amino acid biosynthetic pathway, raising fascinating questions on the yet unknown function of this gene in mammals.

Acetolactate Synthase↗
PubMed1996

Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia.

Stroke is the third leading cause of death, and vascular dementia the second cause of dementia after Alzheimer's disease. CADASIL (for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) causes a type of stroke and dementia whose key features include recurrent subcortical ischaemic events and vascular dementia and which is associated with diffuse white-matter abnormalities on neuroimaging. Pathological examination reveals multiple small, deep cerebral infarcts, a leukoencephalopathy, and a non-atherosclerotic, non-amyloid angiopathy involving mainly the small cerebral arteries. Severe alterations of vascular smooth-muscle cells are evident on ultrastructural analysis. We have previously mapped the mutant gene to chromosome 19. Here we report the characterization of the human Notch3 gene which we mapped to the CADASIL critical region. We have identified mutations in CADASIL patients that cause serious disruption of this gene, indicating that Notch3 could be the defective protein in CADASIL patients.

Adult↗
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

Implications of prenatal diagnosis of sickle cell disease.

Prenatal diagnosis (PND) of sickle cell disease (SCD) has been feasible since about 15 years. The number of PND performed for SCD has constantly increased during these years, but its availability raises difficult ethical questions for parents and counsellors. Concerning at-risk parents, only 50% (data in the literature) to 70% (personal data) ask for PND. Our study shows that mainly cultural reasons, then religious ones, educational level and the number of children in the family weigh on the parents' decision to request this diagnosis. The counsellors' position is difficult since clinical severity of the disease is highly variable, there is no early prognostic factor, and the median life expectancy of patients in industrialized countries exceeds 40 years. We need to define a counselling which would consider the image of the illness in the populations involved, in order to help parents understand the implications of the choice they are asked to make.

Abortion, Eugenic↗
PubMed1995

A gene for hereditary paroxysmal cerebellar ataxia maps to chromosome 19p.

Hereditary paroxysmal cerebellar ataxia (HPCA) is an autosomal dominant disorder characterized by the recurrence of intermittent attacks of vestibulocerebellar ataxia lasting from 15 minutes to a few days. The number of attacks is often significantly decreased by acetazolamide treatment. Neurological examination shows a permanent gaze-evoked nystagmus, as well as a mild cerebellar ataxia in most patients. The paroxysmal feature of this condition is shared by another autosomal dominant neurological condition, familial hemiplegic migraine (FHM), a condition in which permanent cerebellar signs have also been reported in some families. Although hemiplegic migraine has never been reported in patients with HPCA, we hypothesized, based on the latter observations, that HPCA and FHM may be allelic disorders. We previously mapped a gene responsible for FHM on the short arm of chromosome 19. We performed linkage analysis with 6 markers spanning the FHM interval on a large HPCA family. Significant lod scores were obtained with 3 markers: D19S244 (LS = 3.71), D19S221 (3.60), and D19S226 (3.54) at theta = 0. Haplotype and multipoint linkage analysis established that the most likely location was the same interval of 30 cM encompassing the chromosome 19 FHM locus.

Cerebellar Ataxia↗
PubMed1994

Genetic heterogeneity of familial hemiplegic migraine.

Familial hemiplegic migraine (FHM) is an autosomal dominant variety of migraine with aura. We previously mapped a gene responsible for this disorder to the short arm of chromosome 19, within a 30-cM interval bracketed by D19S216 and D19S215. Linkage analysis conducted on two large pedigrees did not show any evidence of heterogeneity, despite their clinical differences due to the presence, in one family, of cerebellar ataxia and nystagmus. Herein we report linkage data on seven additional FHM families including another one with cerebellar ataxia. Analysis was conducted with a set of seven markers spanning the D19S216-D19S215 interval. Two-point and multipoint lod score analyses as well as HOMOG testing provided strong evidence for genetic heterogeneity. Strong evidence of linkage was obtained in two families and of absence of linkage in four families. The posterior probability of being of the linked type was > .95 in the first two families and < .01 in four other ones. It was not possible to draw any firm conclusion for the last family. Thus, within the nine families so far tested, four were linked, including those with associated cerebellar ataxia. We could not find any clinical difference between the pure FHM families regardless of whether they were linked. In addition to the demonstration of genetic heterogeneity of FHM, this study also allowed us to establish that the most likely location of the gene was within an interval of 12 cM between D19S413 and D19S226.

Ataxia↗
PubMedDate not supplied

Age at menarche in Tahiti.

Data on age at menarche have been collected, using the status quo method, among 1246 Tahitian girls attending school. The median age, estimated by probits, is 12.75 SD 1.76. The girls of the rural districts have a higher median age (13.08 SD 1.97) than the girls of Papeete (12.61 SD 1.47). The results were compared with data collected among other girls of Maori or European ancestry in France, New Zealand and Easter Island.

Adolescent↗