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Age at onset prediction in spinocerebellar ataxia type 3 changes according to population of origin
Author(s) -
de Mattos E. P.,
Leotti V. B.,
Soong B.W.,
Raposo M.,
Lima M.,
Vasconcelos J.,
Fussiger H.,
Souza G. N.,
Kersting N.,
Furtado G. V.,
Saute J. A. M.,
Camey S. A.,
SaraivaPereira M. L.,
Jardim L. B.
Publication year - 2019
Publication title -
european journal of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 124
eISSN - 1468-1331
pISSN - 1351-5101
DOI - 10.1111/ene.13779
Subject(s) - medicine , spinocerebellar ataxia , age of onset , clinical neurology , population , pediatrics , ataxia , neuroscience , psychiatry , disease , psychology , environmental health
Background and purpose In spinocerebellar ataxia type 3/Machado–Joseph disease ( SCA 3/ MJD ), the length of CAG repeat expansions in ATXN 3 shows an inverse correlation with age at onset ( AO ). Recently, a formula for predicting AO based on CAG expansion was developed for European carriers. We tested this formula in SCA 3/ MJD carriers from distinct origins and developed population‐specific models to predict AO . Methods This was a parametric survival modelling study. Results The European formula (EF) was tested in 739 independent SCA 3/ MJD carriers from South Brazil, Taiwan and the Portuguese Azorean islands, and it largely underestimated AO in South Brazilian and Taiwanese test cohorts. This finding challenged the universal use of the EF, leading us to develop and validate population‐specific models for AO prediction. Using validation cohorts, we showed that Brazilian and Taiwanese formulas largely outperformed the EF in a population‐specific manner. Inversely, the EF was more accurate at predicting AO among Portuguese Azorean patients. Hence, specific prediction models were required for each SCA 3/ MJD ethnic group. Conclusions Our data strongly support the existence of as yet unknown factors that modulate AO in SCA 3/ MJD in a population‐dependent manner, independent of CAG expansion length. The generated models are made available to the scientific community as they can be useful for future studies on SCA 3/ MJD carriers from distinct geographical origins.