Luciana de Andrade Agostinho

A systematic review of the intergenerational aspects and the diverse genetic profiles of Huntington's disease.

Huntingtons disease (HD) is a rare progressive and fatal neurogenetic degenerative disease, characterized by movement and personality disorders and by progressive dementia. Its prevalence varies by ethnic origin and different genetic profiles predisposing individuals to HD in each population. The prevalence of HD is 5-10 per 100,000 individuals in Caucasian populations of North America and Western Europe. It is an autosomal dominant disease associated with the expansion of CAG-type repetitive DNA sequences in the HTT gene. This gene, located on the short arm of chromosome 4, encodes the protein huntingtin. In this study, we reviewed 17 articles about HD that report data from 2400 affected individuals from various countries around the world, including Venezuela, China, Croatia, Turkey, Germany, Italy, Brazil, Spain, Taiwan, India, the Netherlands, Russia, and the USA, with a focus on genetic profiles and intergenerational expansions or contractions of expanded alleles responsible for causing HD. We discuss the genetic characteristics of HD in different populations and any atypical cases reported in these studies.

Haplotype analysis of the CAG and CCG repeats in 21 Brazilian families with Huntington’s disease

We studied the allelic profile of CAG and CCG repeats in 61 Brazilian individuals in 21 independent families affected by Huntington’s disease (HD). Thirteen individuals had two normal alleles for HD, two had one mutable normal allele and no HD phenotype, and forty-six patients carried at least one expanded CAG repeat allele. Forty-five of these individuals had one expanded allele and one individual had one mutable normal allele (27 CAG repeats) and one expanded allele (48 CAG repeats). Eleven of these forty-five subjects had a mutant allele with reduced penetrance, and thirty-four patients had a mutant allele with complete penetrance. Inter- and intragenerational investigations of CAG repeats were also performed. We found a negative correlation between the number of CAG repeats and the age of disease onset (r=−0.84; P<0.001) and no correlation between the number of CCG repeats and the age of disease onset (r=0.06). We found 40 different haplotypes and the analysis showed that (CCG)10 was linked to a CAG normal allele in 19 haplotypes and to expanded alleles in two haplotypes. We found that (CCG)7 was linked to expanded CAG repeats in 40 haplotypes (95.24%) and (CCG)10 was linked to expanded CAG repeats in only two haplotypes (4.76%). Therefore, (CCG)7 was the most common allele in HD chromosomes in this Brazilian sample. It was also observed that there was a significant association of (CCG)7 with the expanded CAG alleles (χ2=6.97, P=0.0084). Worldwide, the most common CCG alleles have 7 or 10 repeats. In Western Europe, (CCG)7 is the most frequent allele, similarly to our findings.

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

Huntingtons 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.

A Study of a Geographical Cluster of Huntington's Disease in a Brazilian Town of Zona da Mata, Minas Gerais State

Background/Aims: Our aim was to investigate a geographical cluster of Huntingtons disease (HD) in Ervalia, a Brazilian town of Minas Gerais state (MG). Therefore, we calculated the minimum prevalence of HD in Ervalia, known to have many HD affected families. We also determined the genetic profile of the polymorphic CAG region of the HTT gene in 32 subjects of these affected families. Methods: A descriptive cross-sectional study was performed, starting in January 2011 until June 2013. Individuals who participated in the survey were all from Ervalia town, MG. Results: The minimum prevalence rate found was 7.2/10,000 people, higher than the worldwide prevalence. Conclusion: The minimum prevalence of HD in Ervalia was at least 10.3- to 14.4-fold greater than that of the world population, although it does not represent the overall prevalence of the disease in Brazil. Certainly an expanded survey in the country will lead to a lower prevalence estimate than Ervalias.

The CIITA genetic polymorphism rs4774*C in combination with the HLA-DRB1*15:01 allele as a putative susceptibility factor to multiple sclerosis in Brazilian females

The objective of this study was to investigate the association between the HLA alleles at the DQA1, DQB1 and DRB1 loci, the CIITA genetic polymorphisms -168A/G and +1614G/C, and susceptibility to multiple sclerosis (MS) in a sample from Rio de Janeiro State, Brazil. Furthermore, we wished to determine whether any of these associations might be more significant in women compared with men. DNA samples from 52 relapsing-remitting MS (RRMS) patients and 126 healthy controls matched for sex and age were analyzed. We identified a significant HLA-DRB1*15:01-MS association that was female-specific (Odds Ratio (OR) = 4.78; p = 0.001). Furthermore, we observed that the +1614G/C mutation in combination with the HLA-DRB1*15:01 allele increased susceptibility to MS in females (OR = 4.55; p = 0.01). Together, these findings highlight the polygenic nature of MS.

Comparação Entre Eletroforese em Gel de Agarose e Capilar Automatizada na Detecção de Amplificação das Repetições CAG no Gene HTT

Sensitiveness profile of microorganisms in the curimba Prochilodus lineatus (Valenciennes, 1847) was isolated, characterized and evaluated. Fragments of the fish body underwent microbiological analysis whereas microorganisms were isolated to investigate isolation, characteriszation and evaluation of the sensitiveness profile. Pseudomonas aeruginosa and Enterobacter cloacae were the organisms found, featuring resistance to three out of the eight antibiotics tested.