Spinocerebellar ataxias in Brazil--frequencies and modulating effects of related genes.
This study describes the frequency of spinocerebellar ataxias and of CAG repeats range in different geographical regions of Brazil, and explores the hypothetical role of normal CAG repeats at ATXN1, ATXN2, ATXN3, CACNA1A, and ATXN7 genes on age at onset and on neurological findings. Patients with symptoms and family history compatible with a SCA were recruited in 11 cities of the country; clinical data and DNA samples were collected. Capillary electrophoresis was performed to detect CAG lengths at SCA1, SCA2, SCA3/MJD, SCA6, SCA7, SCA12, SCA17, and DRPLA associated genes, and a repeat primed PCR was used to detect ATTCT expansions at SCA10 gene. Five hundred forty-four patients (359 families) were included. There were 214 SCA3/MJD families (59.6 %), 28 SCA2 (7.8 %), 20 SCA7 (5.6 %), 15 SCA1 (4.2 %), 12 SCA10 (3.3 %), 5 SCA6 (1.4 %), and 65 families without a molecular diagnosis (18.1 %). Divergent rates of SCA3/MJD, SCA2, and SCA7 were seen in regions with different ethnic backgrounds. 64.7 % of our SCA10 patients presented seizures. Among SCA2 patients, longer ATXN3 CAG alleles were associated with earlier ages at onset (p < 0.036, linear regression). A portrait of SCAs in Brazil was obtained, where variation in frequencies seemed to parallel ethnic differences. New potential interactions between some SCA-related genes were presented.
Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, 90.035-903, Porto Alegre, Rio Grande do Sul, Brazil.
Raphael Machado
RM
de Castilhos
Gabriel Vasata
GV
Furtado
Tailise Conte
TC
Gheno
Paola
P
Schaeffer
Aline
A
Russo
Orlando
O
Barsottini
José Luiz
JL
Pedroso
Diego Z
DZ
Salarini
Fernando Regla
FR
Vargas
Maria Angélica de Faria Domingues
MA
de Lima
Clécio
C
Godeiro
Luiz Carlos
LC
Santana-da-Silva
Maria Betânia Pereira
MB
Toralles
Silvana
S
Santos
Hélio
H
van der Linden
Hector Yuri
HY
Wanderley
Paula Frassineti Vanconcelos
PF
de Medeiros
Eliana Ternes
ET
Pereira
Erlane
E
Ribeiro
Maria Luiza
ML
Saraiva-Pereira
Laura Bannach
LB
Jardim
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000067699:Ataxin-3; D001938:Brazil / Q000453:epidemiology; D002648:Child; D004252:DNA Mutational Analysis; D005190:Family; D006801:Humans; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D010641:Phenotype; D044469:Racial Groups / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D012640:Seizures / Q000453:epidemiology / Q000235:genetics; D020754:Spinocerebellar Ataxias / Q000453:epidemiology* / Q000235:genetics*; D019680:Trinucleotide Repeat Expansion; D055815:Young Adult
D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; C092341:ATXN3 protein, human; D000067699:Ataxin-3