Epidemiological, clinical, and molecular characterization of Cuban families with spinocerebellar ataxia type 3/Machado-Joseph disease.
BACKGROUND
Spinocerebellar Ataxia Type 3/Machado-Joseph Disease (SCA3/MJD) is a hereditary neurodegenerative disorder resulting from the expansion of CAG repeats in the ATXN3 gene. It is the most common autosomal dominant ataxia in the world, but its frequency prevalence in Cuba remains uncertain. We undertook a national study in order to characterize the ATXN3 gene and to determine the prevalence of SCA3/MJD in Cuba.


RESULTS
Twenty-two individuals belonging to 8 non-related families were identified as carriers of an expanded ATXN3 allele. The affected families come from the central and western region of the country. Ataxia of gait was the initial symptom in all of the cases. The normal alleles ranged between 14 and 33 CAG repeats while the expanded ones ranged from 63 to 77 repeats. The mean age at onset was 40 ± 9 years and significantly correlated with the number of CAG repeats in the expanded alleles.


CONCLUSIONS
This disorder was identified as the second most common form of spinocerebellar ataxia (SCA) in Cuba based on molecular testing, and showing a different geographical distribution from that of SCA2. This research constitutes the first clinical and molecular characterization of Cuban SCA3 families, opening the way for the implementation of predictive diagnosis for at risk family members.
Centre for the Research and Rehabilitation of Hereditary Ataxias (CIRAH), Libertad Street 26, Holguín, Postal code 80100 Cuba.
Yanetza
Y
González-Zaldívar
Centre for the Research and Rehabilitation of Hereditary Ataxias (CIRAH), Libertad Street 26, Holguín, Postal code 80100 Cuba.
Yaimeé
Y
Vázquez-Mojena
Centre for the Research and Rehabilitation of Hereditary Ataxias (CIRAH), Libertad Street 26, Holguín, Postal code 80100 Cuba.
José M
JM
Laffita-Mesa
Centre for the Research and Rehabilitation of Hereditary Ataxias (CIRAH), Libertad Street 26, Holguín, Postal code 80100 Cuba.
Luis E
LE
Almaguer-Mederos
Centre for the Research and Rehabilitation of Hereditary Ataxias (CIRAH), Libertad Street 26, Holguín, Postal code 80100 Cuba.
Roberto
R
Rodríguez-Labrada
Centre for the Research and Rehabilitation of Hereditary Ataxias (CIRAH), Libertad Street 26, Holguín, Postal code 80100 Cuba.
Gilberto
G
Sánchez-Cruz
Centre for the Research and Rehabilitation of Hereditary Ataxias (CIRAH), Libertad Street 26, Holguín, Postal code 80100 Cuba.
Raúl
R
Aguilera-Rodríguez
Centre for the Research and Rehabilitation of Hereditary Ataxias (CIRAH), Libertad Street 26, Holguín, Postal code 80100 Cuba.
Tania
T
Cruz-Mariño
Centre for the Research and Rehabilitation of Hereditary Ataxias (CIRAH), Libertad Street 26, Holguín, Postal code 80100 Cuba.
Nalia
N
Canales-Ochoa
Division of Medical Genetics, Department of Pathology, Laboratory Medicine and Medical Genetics, Victoria General Hospital, Victoria, Canada.
Patrick
P
MacLeod
Centre for the Research and Rehabilitation of Hereditary Ataxias (CIRAH), Libertad Street 26, Holguín, Postal code 80100 Cuba.
Luis
L
Velázquez-Pérez
CAG repeats; Machado-Joseph Disease; SCA3/MJD; Spinocerebellar ataxia type 3