Full text
| |
| Author(s): |
Lúcia Inês Macedo de Souza
Total Authors: 1
|
| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Instituto de Biociências (IBIOC/SB) |
| Defense date: | 2008-08-22 |
| Examining board members: |
Mayana Zatz;
Luciana Amaral Haddad;
Laura Bannach Jardim;
Fernando Kok;
Paulo Alberto Otto
|
| Advisor: | Mayana Zatz |
| Abstract | |
We studied two large families with expressions of neurodegenerative diseases. One is from the high west of the state of Rio Grande do Norte and the other from São José do Rio Preto region, in São Paulo. The first, an extended family with a tradition of consanguineous marriages, has 68 individuals affected by the syndrome named by us Spoan (Spastic Paraplegia, Optic Atrophy, Neuropathy). The Spoan syndrome is a neurodegenerative disease, autosomal recessive, characterized by congenital Optic Atrophy, spasticity, axonal polyNeuropathy peripheral sensory-motor, shocks to the sound stimuli, joint and spine deformities, and dysarthria. These results were published in 2005 in Ann Neurol. 57 (5):730-7. Latter we analyzed 23 genes that were entirely sequenced. No mutation was observed. Samples of 65 affected and their relatives were studied for six microsatellite markers, totaling 149 individuals genotiped. Fifty single nucleotide polymorphisms (SNPs), located in the critical region, were also investigated, which allowed us to reduce the region for the SPOAN gene from 4.8 to 2.3 Mb, between the SNP rs1939212 and microsatellite D11S987 in 11q13. All patients are homozygous only at D11S1889, which two-point lod score with a Zmax of 27 at .=0.0 was obtained. The results of this study are being submitted. The second family was studied by Dr. Mayana Zatz group a few years ago. We investigated 12 affected and 12 normal relatives. Among these, seven patients, aged between 30 and 60 years, were clinically evaluated. The age of onset was from the third decade of life and disease showed behaviour very uniform, all affected showed Spastic Paraplegia as the only symptom. For the marker DXS8057, in Xq25, was obtained a maximum lod score of 4.13 at .=0.0. The candidate region was maped between the markers DXS1001 and DXS8033, about 14Mb and demonstrate the existence of a new gene locus on chromosome X, named by us SPG34. The results of this study were published in Neurogenet on line on may.08.2008. (AU) | |