Clinical and genetic features of families with frontotemporal dementia and parkinsonism linked to chromosome 17 with a P301S tau mutation.

In 9 patients with frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) with a P301S tau mutation, the predominant phenotype was frontotemporal dementia in 3 and parkinsonism in 6. Comparison of the tau genotype/haplotype carrying the mutation and the initial clinical sign showed association between H1/H1 and parkinsonism and between H1/H2 and personality change. Thus, the tau haplotype carrying the mutation and the tau genotype may be related to the clinical phenotype throughout the disease course.

Filial maturity as a predictor for the burden of demented parents' caregivers.

In this study, we administered the Louvain Filial Maturity Scale [Marcoen 1993] to 61 adult children of demented elderly. The scores of the seven factors of this scale were compared to the scores of an unselected group of adult children examined by Marcoen. The results were taken into the context with caregiver's burden, and the effect of filial maturity on parents' institutionalisation was investigated. Marcoen's results were confirmed. Only the means of "filial help" and "parental consideration" differed slightly from the means of the unselected group. Overall, filial maturity had no influence on the caregiver's feeling of burden, but higher "parental consideration" resulted in lower caregiver burden. In addition, adult children with more "filial obligation" continued to care for their parents in the community more often, even when experiencing great burden and stress. However, institutionalisation was caused mainly by parents' growing needs and increasing behavioural problems. We conclude that "filial maturity" seems to be a very stable concept. Further investigations should focus on the relevance of the Louvain Filial Maturity Scale for caregiving relationship and also on the arrangement of the scale in order to exclude a "pseudo"-stability with regard to burdensome life events and situations.

Differential cellular expression of the human MSH2 protein in normal and myelodysplastic haematopoiesis.

Loss of human MSH2 (hMSH2) protein might be involved in the multistep pathogenesis of haematological malignancies associated with genetic instability. Here, we examine cellular hMSH2 expression in bone marrow samples from 10 haematopoietically normal individuals in comparison with nine patients with myelodysplastic syndrome (MDS) [one refractory anaemia (RA), two RA with ringed sideroblasts (RARS), four RA with excess blasts (RAEB) and two RAEB in transformation (RAEB-T)]. HMSH2 protein was predominantly expressed in myeloblasts and promyelocytes. Blast cells from three patients with RAEB and one with RAEB-T displayed absent or very low hMSH2 expression. As no correlation between hMSH2 expression and chromosomal aberrations was observed, further genetic events seem to be required to induce karyotype instability.

Genetic instability in myelodysplastic syndrome: detection of microsatellite instability and loss of heterozygosity in bone marrow samples with karyotype alterations.

Using a polymerase chain reaction (PCR)-based approach, we examined the prevalence of loss of heterozygosity (LOH) and microsatellite instability (MSI) in relation to chromosomal imbalances in myelodysplastic syndrome (MDS). Two of 26 patients displayed MSI (8%), one of them at five loci. LOH was detected in six out of 26 cases (23%), predominantly involving markers IRF1 [5q31] and WT1 [11p]. Two patients displayed a corresponding chromosomal deletion by conventional cytogenetics. Supporting the mutator phenotype hypothesis, a significant coincidence of LOH, MSI and chromosome abnormalities was observed (P < 0.025). Moreover, our data suggest that LOH represents an initial rather than a secondary genetic event in MDS, promoting genetic instability in a subset of patients.