Clin Genet 2013: 84: 382 – 385 Printed in Singapore. All rights reserved  2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd CLINICAL GENETICS doi: 10.1111/cge.12070 Short Report New evidence for, and challenges in, linking small CGG repeat expansion FMR1 alleles with Parkinson’s disease Loesch DZ, Tassone F, Lo J, Slater HR, Hills LV, Bui MQ, Silburn PA, Mellick GD. New evidence for, and challenges in, linking small CGG repeat expansion FMR1 alleles with Parkinson’s disease. Clin Genet 2013: 84: 382–385.  John Wiley & Sons A/S. Published by John Wiley & Sons Ltd, 2012 We recently reported a significant increase in the frequency of carriers of grey zone (GZ) alleles of FMR1 gene in Australian males with Parkinson’s disease (PD) from Victoria and Tasmania. Here, we report data comparing an independent sample of 817 PD patients from Queensland to 1078 consecutive Australian male newborns from Victoria. We confirmed the earlier finding by observing a significant excess of GZ alleles in PD (4.8%) compared to controls (1.5%). Although both studies provided evidence in support of an association between GZ-carrier status and increased risk for parkinsonism, the existing evidence in the literature from screening studies remains equivocal and we discuss the need for alternative approaches to resolve the issue. Conflict of interest Nothing to declare. DZ Loesch a , F Tassone b,c , J Lo b , HR Slater d , LV Hills d , MQ Bui e , PA Silburn f and GD Mellick g a School of Psychological Science, La Trobe University, Bundoora, Victoria, Australia, b Department of Biochemistry and Molecular Medicine, School of Medicine, University of California Davis, Davis, CA, USA, c Medical Investigation of Neurodevelopmental Disorders (M.I.N.D.) Institute, University of California Davis Medical Center, Sacramento, CA, USA, d VCGS Cytogenetics Laboratory, Murdoch Childrens Research Institute, Royal Children’s Hospital, Parkville, Australia, e Centre for Molecular, Environmental, Genetic, and Analytic Epidemiology, University of Melbourne, Parkville, Victoria, Australia, f Centre for Clinical Research, University of Queensland, Herston, Australia, and g Eskitis Institute for Cell and Molecular Therapies, Griffith University, Queensland, Brisbane, Australia Key words: CGG repeat – FMR1 gene – fragile X – grey zone alleles – Parkinson’s disease – screening results Corresponding author: Dr Danuta Loesch, School of Psychological Science, La Trobe University, Bundoora, Victoria 3086, Australia. Tel.: +61 3 94791382; fax: +61 3 94791956; e-mail: d.loesch@latrobe.edu.au Received 20 September 2012, revised and accepted for publication 19 November 2012 Fragile X-associated tremor/ataxia syndrome (FXTAS) (1) is a progressive late-onset neurodegenerative disorder associated with the pre-mutation (PM) allele of the fragile X mental retardation (FMR1 ) gene, which contains small expansions of CGG repeat in the promoter region ranging 55–200 (2). Characteristic features of FXTAS are intention tremor, ataxia and cog- nitive decline (1, 3–5), with parkinsonian symptoms occurring in nearly half of the affected individuals (3). The underlying neuropathology comprises widespread 382