Ataxin-2 polyQ expansions in FTLD-ALS spectrum disorders in Flanders-Belgian cohorts.
There exists considerable clinical and pathological overlap between frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS), which implies that these 2 neurodegenerative conditions share common pathogenic mechanisms. Recently, intermediate-length (27-33) polyglutamine (polyQ) expansions in ataxin-2 (ATXN2) have been associated with increased risk for ALS, while expansions of > 34 repeats are known to cause spinocerebellar ataxia type 2 (Sca-2). We identified in 72 ALS patients one patient with a 33 polyQ expansion that was absent in 810 control individuals. This allele was also found in one patient with concomitant ALS-Sca-2. In contrast, in a Flanders-Belgian series of 270 FTLD and 22 FTLD-ALS patients, we found no association with intermediate-length polyQ expansions nor did we observe patient-specific long expansions in agreement with the recent observation in a screening of a substantial sized cohort of patients with diverse neurodegenerative brain diseases. Our results provide further support to the notion that ATXN2 associated polyglutamine amplification is specific to the ALS-end of the FTLD-ALS disease spectrum.
Department of Molecular Genetics, VIB, Universiteitsplein 1, Antwerpen, Belgium.
Tim
T
Van Langenhove
Julie
J
van der Zee
Sebastiaan
S
Engelborghs
Rik
R
Vandenberghe
Patrick
P
Santens
Marleen
M
Van den Broeck
Maria
M
Mattheijssens
Karin
K
Peeters
Dirk
D
Nuytten
Patrick
P
Cras
Peter P
PP
De Deyn
Peter
P
De Jonghe
Marc
M
Cruts
Christine
C
Van Broeckhoven
D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000453:epidemiology* / Q000208:ethnology / Q000235:genetics*; D000067528:Ataxins; D001530:Belgium / Q000453:epidemiology; D015331:Cohort Studies; D042622:DNA Repeat Expansion / Q000235:genetics*; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000453:epidemiology* / Q000208:ethnology / Q000235:genetics*; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*
D000067528:Ataxins; D009419:Nerve Tissue Proteins