Clinical and genetic characteristics of Mexican Huntington's disease patients

Alonso, María Elisa; Ochoa, Adriana; Boll, Marie‐Catherine; Sosa, Ana Luisa; Yescas, Petra; López, Marisol López; Macías, Rosario Márquez; Familiar, Itziar; Rasmussen, Astrid

doi:10.1002/mds.22737

Cited by 40 publications

(37 citation statements)

References 14 publications

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“…Expansion of an IA to the complete penetrant allele was observed in two cases: one father bearing 34 CAG repeats transmitted an allele with 45 repeats to his child, as well as a father with 35 repeats transmitted an allele with 71 repeats. In this study the average of CAG repeats was 19.04 among the normal alleles and 47.16 among the expanded ones (Alonso et al, 2009).…”

Section: Resultsmentioning

confidence: 44%

“…The number of CAG repeats in normal chromosomes is significantly higher in populations presenting high prevalence of HD Squitieri et al, 1994). Higher averages of CAG numbers in normal chromosomes were found in Mexico, Cuba, Brazil, Europe, North America, and Oceania (Raskin et al, 2000;Wexler et al, 2004;McNicoll et al, 2008;Alonso et al, 2009;Semaka et al, 2013b;Vázquez-Mojena et al, 2013).…”

Section: Discussionmentioning

confidence: 91%

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REVIEW-ARTICLE Intermediate alleles of Huntington’s disease HTT gene in different populations worldwide: a systematic review

2017

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ABSTRACT. Huntington's disease (HD) is an autosomal dominant progressive neurodegenerative disorder caused by a dynamic mutation due to the expansion of CAG repeats in the HTT gene (4p16.3). The considered normal alleles have less than 27 CAG repeats. Intermediate alleles (IAs) show 27 to 35 CAG repeats and expanded alleles have more than 35 repeats. The IAs apparently have shown a normal phenotype. However, there are some reported associations between individuals that bear an IA and clinical HD signs, such as behavioral disturbs. The association of IAs with the presence of clinical signs gives clinical relevance to these patients. We emphasized the importance of determining the frequency of IA alleles in the general population as well as in HD families. Therefore, the aim of this study was to conduct a systematic review, in order to investigate the frequency of IAs in the overall chromosomes of different ethnic groups and of families with HD history worldwide as well as the frequency of individuals who bear the intermediate alleles. We searched indexed articles from the following electronic databases: U.S. National Library of Medicine and the National Institutes of Health (PubMed), Pubmed Central (PMC) and Virtual Health Library (VHL). Therefore, 488 articles were obtained and, of these, 33 had been published in more than one database. We accepted the article of only one database and ended up with 455 articles for this review. The frequency of IAs within the chromosomes of the general population ranged from 0.45 to 8.7% and of individuals with family history of HD ranged from 0.05 to 5.1%. The higher frequency of IAs in the general population (8.7%) was found in one Brazilian cohort.

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Section: Resultsmentioning

confidence: 44%

Section: Discussionmentioning

confidence: 91%

REVIEW-ARTICLE Intermediate alleles of Huntington’s disease HTT gene in different populations worldwide: a systematic review

2017

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“…In a series of 373 families with Huntington disease followed over 14 years at the INNN, only 11.5% had one or more individuals that underwent presymptomatic testing, in contrast with 58% of the at-risk VHL disease family members (p < 0.001). This difference in uptake of presymptomatic genetic testing is most likely attributable to the lack of preventive and therapeutic options available in Huntington disease [24,25]. …”

Section: Discussionmentioning

confidence: 99%

Uptake of genetic testing and long-term tumor surveillance in von Hippel-Lindau disease

et al. 2010

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Backgroundvon Hippel-Lindau (VHL) disease is a hereditary cancer syndrome caused by germline mutations in the VHL gene. Patients have significant morbidity and mortality secondary to vascular tumors. Disease management is centered on tumor surveillance that allows early detection and treatment. Presymptomatic genetic testing is therefore recommended, including in at-risk children.MethodsWe tested 17 families (n = 109 individuals) for VHL mutations including 43 children under the age of 18. Personalized genetic counseling was provided pre and post-test and the individuals undergoing presymptomatic testing filled out questionnaires gathering socio-demographic, psychological and psychiatric data. Mutation analysis was performed by direct sequencing of the VHL gene. Mutation-carriers were screened for VHL disease-related tumors and were offered follow-up annual examinations.ResultsMutations were identified in 36 patients, 17 of whom were asymptomatic. In the initial screening, we identified at least one tumor in five of 17 previously asymptomatic individuals. At the end of five years, only 38.9% of the mutation-carriers continued participating in our tumor surveillance program. During this time, 14 mutation carriers developed a total of 32 new tumors, three of whom died of complications. Gender, education, income, marital status and religiosity were not found to be associated with adherence to the surveillance protocol. Follow-up adherence was also independent of pre-test depression, severity of disease, or number of affected family members. The only statistically significant predictor of adherence was being symptomatic at the time of testing (OR = 5; 95% CI 1.2 - 20.3; p = 0.02). Pre-test anxiety was more commonly observed in patients that discontinued follow-up (64.7% vs. 35.3%; p = 0.01).ConclusionsThe high initial uptake rate of genetic testing for VHL disease, including in minors, allowed the discontinuation of unnecessary screening procedures in non mutation-carriers. However, mutation-carriers showed poor adherence to long-term tumor surveillance. Therefore, many of them did not obtain the full benefit of early detection and treatment, which is central to the reduction of morbidity and mortality in VHL disease. Studies designed to improve adherence to vigilance protocols will be necessary to improve treatment and quality of life in patients with hereditary cancer syndromes.

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“…HD is notably rare in Finland and Japan, but data for Eastern Asia, Africa and Black Americans are inadequate [34]. There are well-known large populations of patients with HD in Scotland and the Lake Maracaibo region of Venezuela [35,36].…”

Section: Introductionmentioning

confidence: 99%