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1.
Clin Genet ; 94(3-4): 346-350, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29756284

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 , Masculino
2.
J Neurol Sci ; 341(1-2): 41-5, 2014 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-24780439

RESUMO

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 Jovem
4.
Clin Genet ; 83(6): 518-24, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23495852

RESUMO

Having reported the world's highest prevalence of spinocerebellar ataxia type 2 (SCA2), health professionals in Cuba developed a program for the predictive testing of this condition. Between February 2001 and December 2011, a total of 1050 individuals requested their inclusion in the presymptomatic testing (PST) program. Their medical records were retrospectively analyzed in the present descriptive study. A total of 768 participants completed the protocol, 204 withdrew and 78 were excluded. The PST uptake was 24.91%. Females predominated and 70.96% had negative test results. Their main motivations were risk assessment in their descendants, physical and psychological preparation to cope with the disease and planning for the future. The profile of Cuban participants in the predictive testing program is similar to the one reported for other programs all over the world, nevertheless the genetic counseling practice at the community level is a distinctive aspect, which is valuable in providing at-risk individuals with wide and proper knowledge before their testing inclusion request. The SCA2 predictive testing program has high uptake rates and is renowned in our population. Future research is needed to assess the long-term psychological impact in the participants, their partners and relatives.


Assuntos
Predisposição Genética para Doença/genética , Testes Genéticos/métodos , Ataxias Espinocerebelares/diagnóstico , Ataxias Espinocerebelares/genética , Adaptação Psicológica , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cuba/epidemiologia , Saúde da Família , Feminino , Aconselhamento Genético/psicologia , Aconselhamento Genético/estatística & dados numéricos , Predisposição Genética para Doença/psicologia , Testes Genéticos/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Medição de Risco , Ataxias Espinocerebelares/epidemiologia , Revelação da Verdade , Adulto Jovem
6.
Clin Genet ; 78(2): 169-74, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20095980

RESUMO

Previous studies have investigated the close association that exists between CAG repeat number and the age at onset in SCA2 = spinocerebellar ataxia type 2. These studies have focused on affected individuals. To further characterize this association and estimate the risk of a carrier developing SCA2 at a particular age as a function of a specific CAG repeat size, we have analyzed a large group of 924 individuals, including 394 presymptomatic and 530 affected individuals with a CAG repeat length of 32-79 units. Using a Kaplan-Meier survival analysis, we obtained cumulative probability curves for disease manifestation at a particular age for each CAG repeat length in the 34-45 range. These curves were significantly different (p < 0.001) and showed small overlap. All these information may be very valuable in predictive-testing programs, in the planning of studies for the identification of other genetic and environmental factors as modifiers of age at onset, and in the design of clinical trials for people at enlarged risk for SCA2.


Assuntos
Ataxias Espinocerebelares/epidemiologia , Adolescente , Adulto , Idade de Início , Idoso , Criança , Pré-Escolar , Cuba/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ataxias Espinocerebelares/genética , Análise de Sobrevida , Expansão das Repetições de Trinucleotídeos/genética
7.
J Neurol Neurosurg Psychiatry ; 79(3): 315-7, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17951282

RESUMO

OBJECTIVE: To evaluate the significance of antigliadin antibodies (AGA) levels for spinocerebellar ataxia type 2. METHODS: We determined AGA levels in 64 patients with spinocerebellar ataxia type 2 and in 65 healthy matched controls. The clinical assessment was carried out using the International Cooperative Ataxia Rating Scale and CAG repeat number was assessed by PCR. RESULTS: Antibodies were positive in 23.4% of the ataxia patients and 9.09% of the controls. Statistical comparison using chi2 test with Yates's correction reveals significant differences between these two groups (chi2 = 3.94; p = 0.047). The same was obtained for strongly positive AGA (chi2 = 4.62; p = 0.032). There were no significant differences between AGA positive and AGA negative patients in age at onset, disease duration, ataxia score or CAG repeat number, neither in the prevalence of gastrointestinal symptoms, prevalence of wheat intolerance or body weight. CONCLUSIONS: These results demonstrate an association between antigliadin antibodies serum levels and SCA2. However, more work has to be done to clarify the clinical consequences of such an association.


Assuntos
Anticorpos/sangue , Gliadina/imunologia , Ataxias Espinocerebelares/imunologia , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Cuba , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência
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