Evaluation of the role of FMR1 CGG repeat allele in Parkinson’s disease from the Chinese population

Published on July 31, 2023

Imagine you’re a detective investigating a crime. You’ve got two main suspects in mind – FMR1 premutation and the GZ allele of FMR1 CGG repeat expansions – and you’re determined to find out if they’re connected to your case, Parkinson’s disease (PD). In this study, Chinese researchers join the investigation by examining a large group of PD patients and healthy controls. Using a technique called repeat-primed polymerase chain reaction (RP-PCR), they identify two PD patients with FMR1 premutation and eleven with the GZ allele. However, despite this discovery, they ultimately conclude that the GZ allele is not significantly more prevalent in PD cases compared to healthy controls. So, while one suspect – FMR1 premutation – may indeed be linked to PD, the case against the GZ allele remains unsolved. To solve this mystery once and for all, future studies encompassing larger sample sizes and multiple ethnicities are needed. Ready to dive deeper into the evidence? Check out the full research article!

ObjectiveThere is controversial evidence that FMR1 premutation or “gray zone” (GZ) allele (small CGG expansion, 45–54 repeats) was associated with Parkinson’s disease (PD). We aimed to explore further the association between FMR1 CGG repeat expansions and PD in a large sample of Chinese origin.MethodsWe included a cohort of 2,362 PD patients and 1,072 controls from the Parkinson’s Disease and Movement Disorders Multicenter Database and Collaborative Network in China (PD-MDCNC) in this study and conducted repeat-primed polymerase chain reaction (RP-PCR) for the size of FMR1 CGG repeat expansions.ResultsTwo PD patients were detected with FMR1 premutation (61 and 56 repeats), and the other eleven PD patients were detected with the GZ allele of FMR1 CGG repeat expansions. Those thirteen PD patients responded well to levodopa and were diagnosed with clinically established PD. Specifically, one female PD patient with GZ allele was also found with premature ovarian failure. However, compared to healthy controls, we found no significant enrichment of GZ allele carriers in PD patients or other subgroups of PD cases, including the subgroups of female, male, early-onset, and late-onset PD patients. Furthermore, we did not find any correlation between the FMR1 gene CGG repeat sizes and age at onset of PD.ConclusionIt suggested that FMR1 premutation was related to PD, but the GZ allele of FMR1 CGG repeat expansions was not significantly enriched in PD cases of Chinese origin. Further larger multiple ethnic studies are needed to determine further the role of the FMR1 GZ allele in PD.

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