Publication
High germinal instability of the (CTG)n at the SCA8 locus of both expanded and normal alleles
| dc.contributor.author | Silveira, I. | |
| dc.contributor.author | Afonso, I. | |
| dc.contributor.author | Guimarães, L. | |
| dc.contributor.author | Mendonça, P. | |
| dc.contributor.author | Santos, C. | |
| dc.contributor.author | Maciel, P. | |
| dc.contributor.author | Matos, J. | |
| dc.contributor.author | Costa, M. | |
| dc.contributor.author | Barbot, C. | |
| dc.contributor.author | Tuna, A. | |
| dc.contributor.author | Barros, J. | |
| dc.contributor.author | Jardim, L. | |
| dc.contributor.author | Coutinho, P. | |
| dc.contributor.author | Sequeiros, J. | |
| dc.date.accessioned | 2014-02-17T13:16:51Z | |
| dc.date.available | 2014-02-17T13:16:51Z | |
| dc.date.issued | 2000-03 | |
| dc.description.abstract | Abstract The autosomal dominant spinocerebellar ataxias (SCAs) are a group of late-onset, neurodegenerative disorders for which 10 loci have been mapped (SCA1, SCA2, SCA4-SCA8, SCA10, MJD, and DRPLA). The mutant proteins have shown an expanded polyglutamine tract in SCA1, SCA2, MJD/SCA3, SCA6, SCA7, and DRPLA; a glycine-to-arginine substitution was found in SCA6 as well. Recently, an untranslated (CTG)n expansion on chromosome 13q was described as being the cause of SCA8. We have now (1) assessed the repeat size in a group of patients with ataxia and a large number of controls, (2) examined the intergenerational transmission of the repeat, and (3) estimated the instability of repeat size in the sperm of one patient and two healthy controls. Normal SCA8 chromosomes showed an apparently trimodal distribution, with classes of small (15-21 CTGs), intermediate (22-37 CTGs), and large (40-91 CTGs) alleles; large alleles accounted for only0.7% of all normal-size alleles. No expanded alleles (>/=100 CTGs) were found in controls. Expansion of the CTG tract was found in five families with ataxia; expanded alleles (all paternally transmitted) were characterized mostly by repeat-size contraction. There was a high germinal instability of both expanded and normal alleles: in one patient, the expanded allele (152 CTGs) had mostly contraction in size (often into the normal range); in the sperm of two normal controls, contractions were also more frequent, but occasional expansions into the upper limit of the normal size range were also seen. In conclusion, our results show (1) no overlapping between control (15-91) and pathogenic (100-152) alleles and (2) a high instability in spermatogenesis (both for expanded and normal alleles), suggesting a high mutational rate at the SCA8 locus. | por |
| dc.description.sponsorship | We thank Dr. M. Koob for providing us with positive controls for the SCA8 expansion.We are also particularly indebted to Dr. Vaz Oso´ rio (IGM), for supplying the blood spots on filter paper from the IGM national screening for PKU. C. Cunha was of great help with her secretarial assistance. We also thank the staff of the Neurobiology unit at IBMC for their technical support and all patients and their families for their cooperation. This work was supported by research grants PRAXIS/PSAU/C/SAU/084/96, PRAXIS/PSAU/C/SAU/13226/ 98, and Financiamento Plurianual de Unidades de I&DE, all from F.C.T. (Ministry of Science and Technology, Portugal). I.A., L.G., P.M., and C.S. were the recipients of scholarships from the PRAXIS Program, F.C.T., Portugal. | por |
| dc.identifier.citation | Am J Hum Genet. 2000 Mar;66(3):830-40. | por |
| dc.identifier.issn | 0002-9297 | |
| dc.identifier.uri | http://hdl.handle.net/10400.16/1555 | |
| dc.language.iso | eng | por |
| dc.peerreviewed | yes | por |
| dc.publisher | American Society of Human Genetics | por |
| dc.relation.publisherversion | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1288166/pdf/AJHGv66p830.pdf | por |
| dc.title | High germinal instability of the (CTG)n at the SCA8 locus of both expanded and normal alleles | por |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.citation.conferencePlace | United States of America | por |
| oaire.citation.endPage | 840 | por |
| oaire.citation.issue | 66(3) | por |
| oaire.citation.startPage | 830 | por |
| oaire.citation.title | American journal of human genetics | por |
| oaire.citation.volume | 66 | por |
| rcaap.rights | openAccess | por |
| rcaap.type | article | por |