PS1 Alzheimer's disease family with spastic paraplegia: the search for a gene modifier.

PS1 mutations are associated with classic Alzheimer's disease (AD); however, some families develop AD and spastic paraplegia (SP) with brain pathology characterized by Abeta cotton wool plaques. The authors report a variant AD family with the E280Q PS1 mutation. The fact that the same PS1 mutation can be found in patients with either variant or classic AD argues in favor of the presence of a genetic modifier. The authors have excluded that this modifier effect originates from coding sequence variations in three SP genes or from a second mutation in the other AD genes.

[Genetic monitoring of mutational events in human populations at the DNA level]. / Geneticheskii monitoring populiatsii cheloveka po uchëtu mutatsionnykh sobytii na urovne DNK.

It was elaborated the new method of genetic monitoring of human populations at DNA level. Mutation events in the VNTR regions of DNA were registered by comparison of fingerprint bands after Southern blot-hybridisation. The multilocus minisatellite probe Red4 was used for detection of VNTR. If there is an additional band in the DNA fingerprint of a child in comparison with fingerprints of both parents, it was considered as a new mutation in the germ cell of a parent. The study of the spontaneous level of mutations in the VNTR regions showed that there were no differences in the number of fingerprint bands both between males and females and between parents and children. The average number of bands was equal to 21.59 + 5.63 for the parents, and 21.83 + 5.33 for children. The frequency of mutation (per band/per child) was 0.0081, the number of mutation per individual was 0.178. For registration of two-fold increase of mutation frequency it is necessary to have at least 113 persons (and their parents) in each group, but for a 50% increase at least 304 persons.