The aim of the study was to investigate the potential association of epilepsy and EEG abnormalities with autistic regression and mental retardation. We examined a group of 77 autistic children (61 boys, 16 girls) with an average age of 9.1 +/- 5.3 years. Clinical interview, neurological examination focused on the evaluation of epilepsy, IQ testing, and 21-channel EEG (including night sleep EEG recording) were performed. Normal EEGs were observed in 44.4% of the patients, non-epileptiform abnormal EEGs in 17.5%, and abnormal EEGs with epileptiform discharges in 38.1% of the patients. Epilepsy was found in 22.1% of the subjects. A history of regression was reported in 25.8% of the patients, 54.8% of the sample had abnormal development during the first year of life, and 79.7% of the patients were mentally retarded. Autistic regression was significantly more frequent in patients with epilepsy than in non-epileptic patients (p = 0.003). Abnormal development during the first year of life was significantly associated with epileptiform EEG abnormalities (p = 0.014). Epilepsy correlated significantly with mental retardation (p = 0.001). Although the biological basis and possible causal relationships of these associations remain to be explained, they may point to different subgroups of patients with autistic spectrum disorders.

No abstract

Although spinocerebellar ataxia type 3 (SCA3)/Machado-Joseph disease is the most common type of SCA worldwide, we did not identify any cases of the disease amongst SCA patients in the Czech population. It has been proposed that the prevalence of large normal alleles correlates with the frequency of various types of SCA. We have therefore attempted to resolve the absence of SCA3 in our population by investigating, within 204 normal chromosomes, the frequency and nature of CAG repeats as well as two intragenic polymorphisms. We found that large normal alleles with more than 33 CAG repeats were observed at a frequency of only 0.49%. Whereas most of the expanded alleles worldwide have the CA haplotype, this was the least common (5.4%) variant observed in our study, although it was associated with a larger mean CAG repeat length (26.9). We postulate that the absence of SCA3 in the Czech population might be explained by the lack of large normal alleles and consequently a relatively small reservoir for aberrant CAG expansions at the SCA3 locus.

Spinocerebellar ataxia type 28 (SCA28) is an autosomal dominant neurodegenerative disorder caused by missense AFG3L2 mutations. To examine the occurrence of SCA28 in the Czech Republic, we screened 288 unrelated ataxic patients with hereditary (N = 49) and sporadic or unknown (N = 239) form of ataxia for mutations in exons 15 and 16, the AFG3L2 mutation hotspots. A single significant variant, frameshift mutation c.1958dupT leading to a premature termination codon, was identified in a patient with slowly progressive speech and gait problems starting at the age of 68 years. Neurological examination showed cerebellar ataxia, mild Parkinsonian features with predominant bradykinesia, polyneuropathy of the lower limbs, and cognitive decline. However, other common SCA28 features like pyramidal tract signs (lower limb hyperreflexia, positive Babinski sign), ophthalmoparesis or ptosis were absent. The mutation was also found in a patient's unaffected daughter in whom a targeted examination at 53 years of age revealed mild imbalance signs. RNA analysis showed a decreased ratio of the transcript from the mutated AFG3L2 allele relative to the normal transcript in the peripheral lymphocytes of both patients. The ratio was increased by puromycin treatment, indicating that the mutated transcript can be degraded via nonsense-mediated RNA decay. The causal link between the mutation and the phenotype of the patient is currently unclear but a pathogenic mechanism based on AFG3L2 haploinsufficiency rather than the usual dominant-negative effect of missense AFG3L2 mutations reported in SCA28, cannot be excluded.