A Polish pedigree with Alzheimer's disease determined by a novel mutation in exon 12 of the presenilin 1 gene: clinical and molecular characterization.

The presenilin 1 (PS-1) gene, recently identified on chromosome 14q24.3, is a major gene involved into the autosomal dominant forms of early onset Alzheimer's disease (EOAD). Mutations of the PS-1 gene are responsible for the majority of familial EOAD. We found a novel mutation in a Polish family with EOAD from the Poznan region. The mutation at codon 424 in exon 12 of the PS-1 gene leads to an amino acid substitution Leu-Arg in a transmembrane domain VIII of the presenilin 1 molecule. The change is predicted to have a drastic effect on the protein function because it is associated with a very early age of onset (a range of 30-35 years) and a quick progression (about a 4-5 years duration) of the disease.

Apolipoprotein E genotypes in sporadic early and late-onset Alzheimer's disease.

Recent data have demonstrated that presence of apolipoprotein E (APOE) epsilon *4 allele is a major risk factor of Alzheimer's disease (AD). We determined the APOE genotypes in 64 patients with sporadic probable AD and 43 non-demented aged controls selected from Poznan region and the western part of Poland using the polymerase chain reaction (PCR) followed by the restriction fragment length polymorphism (RFLP) analysis. We confirmed a strong correlation of the APOE epsilon *4 allele with sporadic late-onset AD. In contrast to many previous reports we did not found an association between the APOE epsilon *4 allele and sporadic early-onset AD.

[Combined therapy with lamotrigine++ in primary generalized epilepsy in adult patients]. / Terapia wspomagana lamotrigina w padaczce z napadami pierwotnie uogólnionymi u osób doroslych.

An attempt is presented to use Lamictal (lamotrigine) produced by GlaxoWellcome in 30 patients with primary generalized epilepsy, already taking one of antiepileptic drugs, but refractory to this treatment. The patients were treated with carbamazepine (Amizepin) 600-1200 mg daily or with sodium valproate (Depakine) 1200-1600 mg daily. In the course of add-on therapy patients were receiving in first 4 weeks increasing doses of Lamictal starting from 50 mg or 25 mg (patients treated with sodium valproate). Maintenance dose of lamotrigine was 200 mg daily in two divided doses. The results of first three months of the treatment were generally positive. Half the patients experienced a reduction in seizure count by more than a half, what testify the Lamictal is a valuable medication in the treatment of primary generalized epilepsy. The observed side effects had transitory character.

Screening for presenilin-1 gene mutations by PCR-SSCP analysis in patients with early-onset Alzheimer's disease.

The majority of early-onset familial Alzheimer's disease (EOAD) has been associated with mutations in a novel gene on chromosome 14 which has been termed presenilin-1 gene. We screened for mutations within the presenilin-1 gene in twenty patients with EOAD using a PCR-SSCP analysis. We found three aberrant (mutant?) band patterns for exons 4 and 7 in three unrelated patients.

[Familial metachromatic leukodystrophy as a cause of psychotic manifestations in young adults]. / Rodzinna leukodystrofia metachromatyczna jako przyczyna zaburzen psychicznych u mlodych osób doroslych.

Cases of metachromatic leucodystrophy in brother and sister are presented. The clinical pattern in the female was characterised by the progressing dementia, whereas in the male the first symptom was the manic syndrome. The neurological status was normal. The cases were diagnosed by the demyelination visible in MRI pattern and in the decreased activity of arylsulphatase A in blood leukocytes.