Huntington disease: DNA analysis in brazilian population

Raskin, Salmo; Allan, Nasser; Teive, Hélio A.G.; Cardoso, Francisco; Haddad, Mônica Santoro; Levi, Gilberto; Boy, Raquel; Lerena, Juan; Sotomaior, Vanessa Santos; Janzen-Dück, M.; Jardim, Laura Bannach; Fellander, Flávio R.; Andrade, Luiz Augusto Franco de

doi:10.1590/s0004-282x2000000600001

Cited by 28 publications

(54 citation statements)

References 24 publications

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“…In two cases, the alleles did not vary intergenerationally. 14 In our study, the transmitted CAG alleles had a mean change of 2.75 CAG repeats. This change is higher than that found in a previous study conducted in Venezuela, where the mean intergenerational change was 1.27 repeats.…”

Section: Discussionmentioning

confidence: 47%

“…13 Both the normal and the expanded alleles encountered in our investigation had fewer CAG repeats than those reported in previous Brazilian surveys. 13,14 Although these three investigations focused on Brazilian populations, three ranges of CAG repeat sizes were found, which may reflect a sampling bias. However, it is important to mention that Brazil is a country of continental size and its five demographic regions (North, Northeast, Southeast, South and Central West) have populations with diverse origins, including Europe, Asia and Africa.…”

Section: Discussionmentioning

confidence: 99%

“…Some authors consider alleles that bear 27 to 35 CAG repeats to be normal and non-mutable. [13][14][15] These facts have generated confusion about the size of alleles responsible for causing HD.…”

Section: Discussionmentioning

confidence: 99%

“…14 Another survey of Brazilian patients found that the expanded alleles had 43 to 73 CAG repeats. 13 Both the normal and the expanded alleles encountered in our investigation had fewer CAG repeats than those reported in previous Brazilian surveys.…”

Section: Discussionmentioning

confidence: 99%

“…29 The allelic diversity of CCG repeats is much lower than that of CAG repeats, indicating a lower overall mutation rate. 30 An intergenerational Brazilian study 14 found that five CAG alleles had a greater number of repeats (new expansions) and were inherited paternally, and two new expansions were inherited from the mother. On the other hand, only one CAG allele had fewer repeats (new contraction) and was inherited maternally.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2012

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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 ¼ À0.84; Po0.001) and no correlation between the number of CCG repeats and the age of disease onset (r ¼ 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 (v 2 ¼ 6.97, P ¼ 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.

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Section: Discussionmentioning

confidence: 47%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

et al. 2012

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Biallelic mutations in huntington disease: A new case with just one affected parent, review of the literature and terminology

Uhlmann

Peñaherrera

Robinson

et al. 2015

American J of Med Genetics Pt A

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Patients with biallelic mutations for Huntington disease (HD) are rare. We present a 46-year-old female with two expanded Huntingtin (HTT) alleles with just one known affected parent. This is the first reported patient with molecular studies performed to exclude HTT uniparental disomy (UPD). The proband had biparental inheritance of HTT alleles (42/44 CAG repeats). Given the negative UPD results, the proband's unaffected mother either had a reduced penetrance allele that expanded into the full mutation range during transmission to our patient or an unknown full HTT mutation and died before symptom onset, unlikely given no family history of HD and asymptomatic at age 59. We made the novel observation in our literature review that most patients with biallelic HD did not have two full HTT mutations. Most had one HTT allele that was in the intermediate or reduced penetrance ranges or 40 CAG repeats, the lowest limit of the full mutation range. Although the number of patients is small, when an allele in these size ranges was present, generally the age of HD onset was in the 50s. If the second HTT allele had >45 repeats, then onset was typically 20s-30s. While similar ages of onset have been reported for patients with one or two HTT mutations, patients with biallelic mutations may have later onset if an expanded HTT allele has ≤40 CAG repeats. Finally, we propose that "biallelic mutations" or "compound heterozygosity" are more accurate descriptive terms than "homozygosity" when there are two non-identical expanded HTT alleles.

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Genetic counseling and testing for Huntington's disease: A historical review

Nance

2016

American J of Med Genetics Pt B

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This manuscript describes the ways in which genetic counseling has evolved since John Pearson and Sheldon Reed first promoted "a genetic education" in the 1950s as a voluntary, non-directive clinical tool for permitting individual decision making. It reviews how the emergence of Huntington's disease (HD) registries and patient support organizations, genetic testing, and the discovery of a disease-causing CAG repeat expansion changed the contours of genetic counseling for families with HD. It also reviews the guidelines, outcomes, ethical and laboratory challenges, and uptake of predictive, prenatal, and preimplantation testing, and it casts a vision for how clinicians can better make use of genetic counseling to reach a broader pool of families that may be affected by HD and to ensure that genetic counseling is associated with the best levels of care.

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Huntington disease: DNA analysis in brazilian population

Cited by 28 publications

References 24 publications

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

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

Biallelic mutations in huntington disease: A new case with just one affected parent, review of the literature and terminology

Genetic counseling and testing for Huntington's disease: A historical review

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