TY - JOUR
T1 - Machado Joseph-Disease Is Rare in the Peruvian Population
AU - Cornejo-Olivas, Mario
AU - Solis-Ponce, Lesly
AU - Araujo-Aliaga, Ismael
AU - Milla-Neyra, Karina
AU - Ortega, Olimpio
AU - Illanes-Manrique, Maryenela
AU - Mazzetti, Pilar
AU - Manrique-Enciso, Carla
AU - Cubas-Montecino, Diana
AU - Saraiva-Pereira, Maria Luiza
AU - Jardim, Laura B.
AU - Sarapura-Castro, Elison
N1 - Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2023/12
Y1 - 2023/12
N2 - Spinocerebellar ataxia type 3 or Machado-Joseph disease (MJD/SCA3) is the most prevalent autosomal dominant cerebellar ataxia worldwide, but its frequency varies by geographic region. We describe MJD/SCA3 patients diagnosed in a tertiary healthcare institution in Peru. In a cohort of 341 individuals (253 probands) with clinical ataxia diagnosis, seven MJD/SCA3 probands were identified and their pedigrees extended, detecting a total of 18 MJD/SCA3 cases. Out of 506 alleles from all probands from this cohort, the 23-CAG repeat was the most common ATXN3 allele (31.8%), followed by the 14-CAG repeat allele (26.1%). Normal alleles ranged from 12 to 38 repeats while pathogenic alleles ranged from 64 to 75 repeats. We identified 80 large normal (LN) alleles (15.8%). Five out of seven families declared an affected family member traced back to foreign countries (England, Japan, China, and Trinidad and Tobago). MJD/SCA3 patients showed ataxia, accompanied by pyramidal signs, dysarthria, and dysphagia as well as abnormal oculomotor movements. In conclusion, ATXN3 allelic distribution in non-MJD/SCA3 patients with ataxia is similar to the distribution in normal individuals around the world, whereas LN allele frequency reinforces no correlation with the frequency of MJD/SCA3. Evidence of any atypical MJD/SCA3 phenotype was not found. Furthermore, haplotypes are required to confirm the foreign origin of MJD/SCA3 in the Peruvian population.
AB - Spinocerebellar ataxia type 3 or Machado-Joseph disease (MJD/SCA3) is the most prevalent autosomal dominant cerebellar ataxia worldwide, but its frequency varies by geographic region. We describe MJD/SCA3 patients diagnosed in a tertiary healthcare institution in Peru. In a cohort of 341 individuals (253 probands) with clinical ataxia diagnosis, seven MJD/SCA3 probands were identified and their pedigrees extended, detecting a total of 18 MJD/SCA3 cases. Out of 506 alleles from all probands from this cohort, the 23-CAG repeat was the most common ATXN3 allele (31.8%), followed by the 14-CAG repeat allele (26.1%). Normal alleles ranged from 12 to 38 repeats while pathogenic alleles ranged from 64 to 75 repeats. We identified 80 large normal (LN) alleles (15.8%). Five out of seven families declared an affected family member traced back to foreign countries (England, Japan, China, and Trinidad and Tobago). MJD/SCA3 patients showed ataxia, accompanied by pyramidal signs, dysarthria, and dysphagia as well as abnormal oculomotor movements. In conclusion, ATXN3 allelic distribution in non-MJD/SCA3 patients with ataxia is similar to the distribution in normal individuals around the world, whereas LN allele frequency reinforces no correlation with the frequency of MJD/SCA3. Evidence of any atypical MJD/SCA3 phenotype was not found. Furthermore, haplotypes are required to confirm the foreign origin of MJD/SCA3 in the Peruvian population.
KW - ATXN3
KW - Allelic distribution
KW - MJD/SCA3 phenotype
KW - Machado-Joseph disease
KW - Peruvian ataxic patients
KW - Spinocerebellar ataxia type 3
UR - http://www.scopus.com/inward/record.url?scp=85141194691&partnerID=8YFLogxK
U2 - 10.1007/s12311-022-01491-4
DO - 10.1007/s12311-022-01491-4
M3 - Artículo
AN - SCOPUS:85141194691
SN - 1473-4222
VL - 22
SP - 1192
EP - 1199
JO - Cerebellum
JF - Cerebellum
IS - 6
ER -