Full text
| |
| Author(s): |
Roberto Rozenberg
Total Authors: 1
|
| Document type: | Master's Dissertation |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Instituto de Biociências (IBIOC/SB) |
| Defense date: | 2000-12-19 |
| Examining board members: |
Lygia da Veiga Pereira Carramaschi;
Henrique Krieger;
Carlos Alberto Moreira Filho
|
| Advisor: | Lygia da Veiga Pereira Carramaschi |
| Abstract | |
Tay-Sachs disease (TSD) is an autossomal recessive disease of lysossome storage characterized by progressive nervous degeneration. Children affected by TSD manifest first symptoms around 6 months and die before 5 years of age. TSD is caused by mutations in the HEXA gene, coding for the ? subunit of the hexosaminidase A enzyme. In the absence of the enzyme, its substrate, GM2 ganglioside, accumulates in the neurons of the central nervous cortex. Late onset TSD (chronic form) is a rare variant phenotype with appearance of first symptoms during the second or third decade of life. In the Ashkenazi jewish population, 1 in every 31 individuals is a TSD carrier. The disease incidence (1 in every 4.000 newborns) is 100 times higher in this population. The advent of pre-natal diagnosis for TSD and the development of preventive screening programs massively adopted by Ashkenazi jewish populations led to a 90% decrease in the disease incidence in this group. Three mutations in the HEXA gene are responsible for 98% of the disease incidence in Ashkenazi jews. This lead to the establishment of a DNA test for detection of TSD carriers in this population. The brazilian Ashkenazi jewish populations is around 100.000 individuals. This work aimed to establish the need and the acceptance of a screening program for this population. Specifically, it established the frequency of the 3 most common TSD mutations in a sample of the brazilian jewish population and evaluated the reaction of the community to the offer of a preventive program. This work was undertaken in jewish senior high-school students, in São Paulo and Rio de Janeiro, following the canadian preventive model. From 581 students (>=16 years old) that attended educational sessions, 404 volunteered to the test, indicating a 70% participation rate. According to the data of the consent form, approximately 65% of the chromosomes were associated to Ashkenazi jewish ancestry. The molecular analysis of the 3 most common mutations in the HEXA gene from the 404 participants detected 8 carriers (7 of InsTATC1278 and 1 of IVS12+1), thus indicating a carrier frequency of 1/51. In the Ashkenazi fraction, the estimated carrier frequency is 1 in 33 individuals. Both frequencies are similar to those described for other jewish communities (P>0,05). Based in this findings, it was concluded that the implementation of a screening program for TSD in the brazilian jewish population is feasible. The ethical aspects involved are an essential part of such a program. (AU) | |