Minimal prevalence of Huntington's disease in the South of Brazil and instability of the expanded CAG tract during intergenerational transmissions

被引：0

作者：

de Castilhos, Raphael Machado ^{[1
,14
,15
]}

dos Santos, Jose Augusto ^{[6
,14
]}

Augustin, Marina Coutinho ^{[6
,14
]}

Pedroso, Jose Luiz ^{[7
]}

Barsottini, Orlando ^{[7
]}

Saba, Roberta ^{[7
]}

Ferraz, Henrique Ballalai ^{[7
]}

Godeiro Junior, Clecio ^{[8
]}

Vargas, Fernando Regla ^{[9
,10
]}

Salarini, Diego Zanotti ^{[11
]}

Furtado, Gabriel Vasata ^{[1
,14
]}

Polese-Bonatto, Marcia ^{[2
,14
]}

Rodrigues, Luiza Paulsen ^{[3
,14
]}

Sena, Lucas Schenatto ^{[1
]}

Saraiva-Pereira, Maria Luiza ^{[1
,2
,3
,4
,12
,13
,14
]}

Jardim, Laura Bannach ^{[1
,5
,6
,12
,13
,14
,15
]}

Neurogenetica, Rede ^{[14
]}

机构：

[1] Univ Fed Rio Grande do Sul, Programa Posgrad Genet & Biol Mol, Porto Alegre, RS, Brazil

[2] Univ Fed Rio Grande do Sul, Programa Posgradu Bioquim, Porto Alegre, RS, Brazil

[3] Univ Fed Rio Grande do Sul, Programa Posgrad Biol Celular & Mol, Porto Alegre, RS, Brazil

[4] Univ Fed Rio Grande do Sul, Dept Bioquim, Porto Alegre, RS, Brazil

[5] Univ Fed Rio Grande do Sul, Dept Med Interna, Porto Alegre, RS, Brazil

[6] Univ Fed Rio Grande do Sul, Fac Med, Porto Alegre, RS, Brazil

[7] Univ Fed Sao Paulo UNIFESP, Disciplina Neurol Clin, Escola Paulista Med, Sao Paulo, SP, Brazil

[8] Univ Fed Rio Grande do Norte, Dept Med Integrada, Natal, RN, Brazil

[9] Univ Fed Estado Rio de Janeiro UNIRIO, Hosp Graffiie & Guinle, Rio De Janeiro, RJ, Brazil

[10] Fundacao Oswaldo Cruz, Inst Oswaldo Cruz, Lab Epidemiol Malfonnacoes Congenitas, Rio De Janeiro, RJ, Brazil

[11] Santa Casa Misericordia Sao Paulo, Sao Paulo, SP, Brazil

[12] HCPA, Ctr Pesquisa Expt, Lab Identificacao Genet, Porto Alegre, RS, Brazil

[13] HCPA, Serv Genet Med, Porto Alegre, RS, Brazil

[14] HCPA, Ctr Pesquisa Clin, Rede Neurogenet, Porto Alegre, RS, Brazil

[15] Inst Nacl Genet Med Populat INAGEMP, Porto Alegre, RS, Brazil

来源：

GENETICS AND MOLECULAR BIOLOGY | 2019年 / 42卷 / 02期

关键词：

CAG expansion; Huntington's disease; intergenerational instability; minimal prevalence; AGE-OF-ONSET; REPEAT LENGTH; TRINUCLEOTIDE REPEAT; CLINICAL-FEATURES; GENE; MECHANISMS; FREQUENCY; MUTATION; ALLELES;

D O I：

10.1590/1678-4685-GMB-2018-0032

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Huntington's disease (HD) is due to dominant expansions of the CAG repeat of the HTT gene. Meiotic instability of the (CAG)(n) might impact the disorder frequency. We report on HD minimal prevalence in Rio Grande do Sul (RS) state, Brazil, and on intergenerational instability of the (CAG)(n) in HD families. Symptomatic and at-risk subjects from 179 HD families were ascertained between 2013 and 2016. Clinical, molecular and family history data were obtained. Expanded (CAG)(n) length differences between parent and child (delta-expanded-(CAG)(n)) were calculated. Effect of parental age on the (CAG)(n) instability upon transmission was inferred by correlating delta-expanded-(CAG)(n) between siblings to their age differences. HD minimal prevalence in RS state was estimated as 1.85:100,000 inhabitants. Alleles with (CAG)(27-45) were found on 21/384 non-disease associated chromosomes (5.5%); among 253 expanded alleles, four (1.6%) were within reduced penetrance range with (CAG)(36-39). In 32 direct transmissions, mean instability was larger among paternal than maternal transmissions. In direct transmissions and in 51 sibling pairs, parental age at the time of child birth were not correlated with delta-expanded-(CAG)(n). Briefly, HD prevalence in RS state was lower than those reported for European populations. Expanded (CAG)(n) transmissions were unstable and not associated to parental age.

引用

页码：329 / 336

页数：8