Molecular epidemiology of spinocerebellar ataxias in Cuba: insights into SCA2 founder effect in Holguin.
The objective of this study was to determine the prevalence of hereditary ataxias in Cuba, with a special focus on the clinical and molecular features of SCA2. Clinical assessments were performed by neurological examinations and application of the SARA scale. Molecular analyses of genes SCA1-3, SCA6, SCA17 and DRPLA identified 753 patients with SCA and 7173 asymptomatic relatives, belonging to 200 unrelated families. 86.79% of all SCA patients were affected with SCA2. In the Holguin province, the average population prevalence of SCA2 is 40.18x10(5) inhabitants, with the remarkable figure of 141.66x10(5) in the Baguanos municipality. The high prevalence of the SCA2 mutation in Holguin reflects most likely a founder effect. The stabilization of the prevalence along time suggests the existence of premutated chromosomes with pure CAG, acting as reservoir for further expansions. CAG repeat length correlated inversely with age at onset, accounting for 80% of the variability. Genetic anticipation was observed in the 80% of transmissions. Repeat instability was greater in paternal transmissions whereas CAG expansions without anticipation was observed in 10.97% suggesting the effect of CAA interruptions in the CAG segment, which decrease the toxicity of the abnormal ataxin-2, and/or other protective factors.
Centre for the Research and Rehabilitation of the Hereditary Ataxias, Holguin, Cuba. ataxia@cristal.hlg.sld.cu
Luis
L
Velázquez Pérez
Gilberto Sánchez
GS
Cruz
Nieves
N
Santos Falcón
Luis
L
Enrique Almaguer Mederos
Karel
K
Escalona Batallan
Roberto
R
Rodríguez Labrada
Milena
M
Paneque Herrera
José Miguel
JM
Laffita Mesa
Julio C
JC
Rodríguez Díaz
Raúl Aguilera
RA
Rodríguez
Yanetza
Y
González Zaldivar
Dany
D
Coello Almarales
Dennis
D
Almaguer Gotay
Humberto
H
Jorge Cedeño
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D020132:Anticipation, Genetic; D002648:Child; D002675:Child, Preschool; D003462:Cuba / Q000453:epidemiology; D005260:Female; D018703:Founder Effect; D005787:Gene Frequency; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D015995:Prevalence; D012720:Severity of Illness Index; D020754:Spinocerebellar Ataxias / Q000453:epidemiology* / Q000235:genetics*; D019680:Trinucleotide Repeat Expansion; D055815:Young Adult
D009419:Nerve Tissue Proteins