RESUMO
Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disorder caused by the unstable expansion of a cytosine-adenine-guanine (CAG)/cytosine-adenine-adenine (CAA) repeat in the ATXN2 gene, which normally encodes 22 glutamines (Q22). A large study was conducted to characterize the CAG/CAA repeat intergenerational instability in SCA2 families. Large normal alleles (Q24-31) were significantly more unstable upon maternal transmissions. In contrast, expanded alleles (Q32-750) were significantly more unstable during paternal transmissions, in correlation with repeat length. Significant correlations were found between the instability and the age at conception in paternal transmissions. In conclusion, intergenerational instability at ATXN2 locus is influenced by the sex, repeat length and age at conception of the transmitting parent. These results have profound implications for genetic counseling services.
Assuntos
Fatores Etários , Ataxina-2/genética , Impressão Genômica , Instabilidade Genômica , Ataxias Espinocerebelares/genética , Repetições de Trinucleotídeos , Adulto , Alelos , Feminino , Humanos , MasculinoRESUMO
Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative and incurable hereditary disorder caused by a CAG repeat expansion mutation on ATXN2 gene. The identification of reliable biochemical markers of disease severity is of paramount significance for the development and assessment of clinical trials. In order to evaluate the potential use of glutathione-S-transferase (GST) activity as a biomarker for SCA2, a case-control study in 38 affected, presymptomatic individuals or healthy controls was conducted. An enlarged sample of 121 affected individuals was set to assess the impact of GST activity on SCA2 clinical expression. There was a significant increase in GST activity in affected individuals relative to controls, although sensibility and specificity were not high. GST activity was not significantly influenced by sex, age, disease duration or CAG repeat size and did not significantly influence disease severity markers. These findings show a disruption of in vivo GST activity in SCA2, suggesting a role for oxidative stress in the neurodegenerative process.
Assuntos
Glutationa Transferase/sangue , Fenótipo , Ataxias Espinocerebelares/enzimologia , Adolescente , Adulto , Idoso , Análise de Variância , Ataxinas , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/genética , Sensibilidade e Especificidade , Ataxias Espinocerebelares/genética , Repetições de Trinucleotídeos/genética , Adulto JovemAssuntos
Proteínas do Tecido Nervoso/genética , Ataxias Espinocerebelares/genética , Ataxias Espinocerebelares/mortalidade , Expansão das Repetições de Trinucleotídeos/genética , Ataxinas , Cuba/epidemiologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Ataxias Espinocerebelares/epidemiologia , Taxa de SobrevidaRESUMO
Spinocerebellar ataxia type 2 (SCA2, OMI health, reproductive, financial matters, and183090) belongs to a group of hereditary family planning. Therefore, we undertook a sur-neurodegenerative diseases caused by the expan- vey of the age of onset in a cohort of SCA2sion of a CAG repeat tract in coding regions of patinovel genes. This group includes Huntingtonsdisease (HD), spinal and bulbar muscularatrophy (SBMA), dentatorubral-pallidoluysianatrophy, and the spinocerebellar ataxias type 1,3, 6, 7, and 17 (1). These mutations show a veryhigh penetrance, and they follow an autosomaldominant inheritance pattern with the onlyexception of SBMA (X-linked); each descendantof an affected patient has an a priori risk of 50%.However, it has been proven that the empiric riskof having inherited the mutation causing HD orSCA3 (MachadoJoseph disease) lessens withadvancing age (2, 3). This fact has significantimplications in the genetic counseling of at-riskindividuals. The accuracy and precision that areachieved in the estimate of the risk of developinga certain hereditary illness will have a very...(AU)
