Unstable insertion in the 5' flanking region of the cystatin B gene is the most common mutation in progressive myoclonus epilepsy type 1, EPM1.

Progressive myoclonus epilepsy type 1 (EPM1, also known as Unverricht-Lundborg disease) is an autosomal recessive disorder characterized by progressively worsening myoclonic jerks, frequent generalized tonic-clonic seizures, and a slowly progressive decline in cognition. Recently, two mutations in the cystatin B gene (also known as stefin B, STFB) mapping to 21q22.3 have been implicated in the EPM1 phenotype: a G-->C substitution in the last nucleotide of intron 1 that was predicted to cause a splicing defect in one family, and a C-->T substitution that would change an Arg codon (CGA) to a stop codon (TGA) at amino acid position 68, resulting in a truncated cystatin B protein in two other families. A fourth family showed undetectable amounts of STFB mRNA by northern blot analysis in an affected individual. We present haplotype and mutational analyses of our collection of 20 unrelated EPM1 patients and families from different ethnic groups. We identify four different mutations, the most common of which consists of an unstable approximately 600-900 bp insertion which is resistant to PCR amplification. This insertion maps to a 12-bp polymorphic tandem repeat located in the 5' flanking region of the STFB gene, in the region of the promoter. The size of the insertion varies between different EPM1 chromosomes sharing a common haplotype and a common origin, suggesting some level of meiotic instability over the course of many generations. This dynamic mutation, which appears distinct from conventional trinucleotide repeat expansions, may arise via a novel mechanism related to the instability of tandemly repeated sequences.

Respirometry-based on-line model parameter estimation at a full-scale WWTP.

This paper describes part of a project to develop a systematic approach to knowledge extraction from on-line respirometric measurements in support of wastewater treatment plant control and operation. The paper deals with the following issues: (1) test of the implementation of an automatic set-up consisting of a continuous laboratory respirometer integrated in a mobile trailer with sampling and dosing equipment, and data-acquisition and communication system; (2) assessment of activated sludge/sewage characteristics from sludge respirograms by model parameter estimation; (3) comparison of the parameter estimates with regular plant data and information obtained from supplementary wastewater respirograms. The paper describes the equipment and some of its measuring results from a period of one week at a large-scale wastewater treatment plant. The measurements were evaluated in terms of the common activated sludge modelling practice. The automatic set-up allowed reliable measurements during at least one week. The data were used to calibrate two different version of the model, and independent parameter estimates were obtained.

[A study of 95 families having at least two epileptic children (author's transl)]. / Etude de 95 familles ayant au moins dexu enfants épileptiques.

This report concerns a study of 95 families in which at least two of the children had epilepsy (a total of 210 cases). A total of 45 p. 100 of the patients were from 60 p. 100 of the families and had an intellectual level below the average, and 32 p. 100 of them had an IQ below 70. The family history was the same whether the children were mentally deficient or not. There was no family history of mental deficiency in those families where the epileptic children had a normal IQ but there was a positive family history in 25 p. 100 of families having at least one mentally deficient and epileptic child. The persistence of seizures after 5 years of treatment is seen much more frequently in mentally deficient children than in those with normal intelligence. Finally, the position of the child within the family has no influence and epilepsy may be found in any of the children.

[Photosensitivity and colour filters (a systematic study on 1500 subjects) (author's transl)]. / Photosensibilité et filtres colorés (étude systématique sur 1 500 sujets.

The reinforcing, activating, inhibiting or negative action of yellow, orange, red, green, and blue filters was studied in 1500 patients. A reinforcing action is seen much more frequently in subjects photosensitive to white light who are under twenty years old, while an inhibiting or negative action is more frequent in those over twenty. Two other factors seem to play a role in the reinforcing action of orange and red filters in subjects under twenty years old: epilepsy and cerebral immaturity. None of the non-epileptic subjects who developed a photo-convulsive response to yellow, orange, or red filters only, became epileptic during the two-year follow-up period.

Unverricht-Lundborg disease: absence of nonallelic genetic heterogeneity.

Unverricht-Lundborg disease is a clinically recognizable form of progressive myoclonus epilepsy. Recently, in several families of both Finnish and Mediterranean extraction segregating Unverricht-Lundborg disease, the gene for this disease was linked to the same region of the long arm of chromosome 21. We performed linkage analysis in eight families, including four of neither Baltic nor Mediterranean origin, using a polymorphic (CA)n repeat marker for the human liver-type 6 phosphofructokinase (PFKL) gene, previously mapped to 21q22.3. No recombinations were observed between the disease phenotype and the PFKL marker and a maximum lod score of 5.63 was obtained. These findings confirm tight linkage between PFKL and the gene for Unverricht-Lundborg disease and strongly suggest a lack of nonallelic genetic heterogeneity of the disease.

Mapping of a gene determining familial partial epilepsy with variable foci to chromosome 22q11-q12.

We identified two large French-Canadian families segregating a familial partial epilepsy syndrome with variable foci (FPEVF) characterized by mostly nocturnal seizures arising from frontal, temporal, and occasionally occipital epileptic foci. There is no evidence for structural brain damage or permanent neurological dysfunction. The syndrome is inherited as an autosomal dominant trait with incomplete penetrance. We mapped the disease locus to a 3. 8-cM interval on chromosome 22q11-q12, between markers D22S1144 and D22S685. Using the most conservative diagnostic scheme, the maximum cumulative LOD score was 6.53 at recombination fraction (straight theta) 0 with D22S689. The LOD score in the larger family was 5.34 at straight theta=0 with the same marker. The two families share an identical linked haplotype for >/=10 cM, including the candidate interval, indicating a recent founder effect. A severe phenotype in one of the probands may be caused by homozygosity for the causative mutation, as suggested by extensive homozygosity for the linked haplotype and a bilineal family history of epilepsy. An Australian family with a similar phenotype was not found to link to chromosome 22, indicating genetic heterogeneity of FPEVF.