Familial infantile convulsions and paroxysmal choreoathetosis: a new neurological syndrome linked to the pericentromeric region of human chromosome 16.
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Benign infantile familial convulsions is an autosomal dominant disorder characterized by nonfebrile seizures, with the first attack occurring at age 3-12 mo. It is one of the rare forms of epilepsy that are inherited as monogenic Mendelian traits, thus providing a powerful tool for mapping genes involved in epileptic syndromes. Paroxysmal choreoathetosis is an involuntary-movement disorder characterized by attacks that occur spontaneously or are induced by a variety of stimuli. Classification is still elusive, and the epileptic nature of this movement disorder has long been discussed and remains controversial. We have studied four families from northwestern France in which benign infantile convulsions was inherited as an autosomal dominant trait together with variably expressed paroxysmal choreoathetosis. The human genome was screened with microsatellite markers regularly spaced, and strong evidence of linkage for the disease gene was obtained in the pericentromeric region of chromosome 16, with a maximum two-point LOD score, for D16S3133, of 6.76 at a recombination fraction of 0. Critical recombinants narrowed the region of interest to a 10-cM interval around the centromere. Our study provides the first genetic evidence for a common basis of convulsive and choreoathetotic disorders and will help in the understanding and classification of paroxysmal neurological syndromes. (+info)
Paroxysmal dystonic choreoathetosis. Genetic linkage studies in a British family.
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Paroxysmal dystonic choreoathetosis (PDC) is characterized by attacks of involuntary dystonic and choreoathetoid movements, typically several hours in duration with no sign of abnormality between attacks. Inheritance is autosomal dominant and the PDC locus has recently been assigned to the distal long arm of chromosome 2 in two families. We describe a six-generation British family with PDC and describe the results of fine genetic mapping and candidate gene linkage analysis. As part of a genome-wide search, linkage to chromosome 2q was confirmed in this family. Positive LOD scores were obtained for six markers on 2q. A LOD score of 5.08 at a recombination fraction of 0.0 was obtained for the marker D2S163. Construction of haplotypes allowed definition of a disease interval of 4 cM between the flanking markers D2S295 and D2S377. Polymorphic tandem repeats within the candidate genes CHRND (delta polypeptide of the nicotinic acetylcholine receptor) and SLC4A3 were examined yielding LOD scores of -7.68 and 6.08, respectively, at a recombination fraction of 0.0. This excludes CHRND as a candidate. Our data confirm the assignment of the locus for PDC to chromosome 2q and provide evidence for locus homogeneity in PDC. We have narrowed the disease interval to 4 cM and our findings provide support for the involvement of the gene for the chloride/bicarbonate exchanger as a candidate gene for PDC. (+info)