{"doi":"10.1002/mds.27420","title":"Evidence for the role of <i>FMR1</i> gray zone alleles as a risk factor for parkinsonism in females","abstract":"<jats:title>ABSTRACT</jats:title><jats:p><jats:bold>Background and Objective</jats:bold> There is convincing evidence that small CGG expansion (41‐54 repeats): <jats:italic>FMR1</jats:italic> “gray zone” alleles (GZ) contribute to the risk of parkinsonism in males, but there is insufficient corresponding data in females. This study intends to fill this gap.</jats:p><jats:p><jats:bold>Methods</jats:bold> We screened whole‐blood–derived DNA from a cohort of 601 females diagnosed with idiopathic PD, and from dry Guthrie blood spots from a local sample of 1,005 female newborns (population controls), for the size of the <jats:italic>FMR1</jats:italic> CGG repeat using a PCR technique.</jats:p><jats:p><jats:bold>Results</jats:bold> We found a significant excess (8.2%) of GZ carriers compared with 5.2% in the control sample, with a <jats:italic>P</jats:italic> value of 0.009 for the difference in proportions.</jats:p><jats:p><jats:bold>Conclusion</jats:bold> <jats:italic>FMR1</jats:italic> gray zone alleles are a significant risk factor for parkinsonism in females. These population data and occasional reports of FXTAS‐like or parkinsonian manifestations in carriers suggest possible mechanisms whereby the effects of these alleles synergize with the existing pathologies underpinning parkinsonism. © 2018 International Parkinson and Movement Disorder Society</jats:p>","journal":"Movement Disorders","year":2018,"id":681349,"datarank":0.47670807455219194,"base_score":3.1780538303479458,"endowment":3.1780538303479458,"self_citation_contribution":0.47670807455219194,"citation_network_contribution":0.0,"self_endowment_contribution":0.47670807455219194,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":23,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":349075,"name":"Flora Tassone","orcid":"0000-0002-6388-9180","position":1,"is_corresponding":false},{"id":17427,"name":"George D. Mellick","orcid":"0000-0002-7211-4651","position":2,"is_corresponding":false},{"id":1780164,"name":"Malcolm Horne","orcid":null,"position":3,"is_corresponding":false},{"id":95115,"name":"Justin P. Rubio","orcid":"0000-0003-3750-917X","position":4,"is_corresponding":false},{"id":1780165,"name":"Minh Q. Bui","orcid":null,"position":5,"is_corresponding":false},{"id":96468,"name":"David Francis","orcid":null,"position":6,"is_corresponding":false},{"id":117778,"name":"Elsdon Storey","orcid":null,"position":7,"is_corresponding":false},{"id":820000,"name":"Danuta Z. Loesch","orcid":"0000-0002-2180-2606","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Evidence for the role of <i>FMR1</i> gray zone alleles as a risk factor for parkinsonism in females","abstract":"<jats:title>ABSTRACT</jats:title><jats:p><jats:bold>Background and Objective</jats:bold> There is convincing evidence that small CGG expansion (41‐54 repeats): <jats:italic>FMR1</jats:italic> “gray zone” alleles (GZ) contribute to the risk of parkinsonism in males, but there is insufficient corresponding data in females. This study intends to fill this gap.</jats:p><jats:p><jats:bold>Methods</jats:bold> We screened whole‐blood–derived DNA from a cohort of 601 females diagnosed with idiopathic PD, and from dry Guthrie blood spots from a local sample of 1,005 female newborns (population controls), for the size of the <jats:italic>FMR1</jats:italic> CGG repeat using a PCR technique.</jats:p><jats:p><jats:bold>Results</jats:bold> We found a significant excess (8.2%) of GZ carriers compared with 5.2% in the control sample, with a <jats:italic>P</jats:italic> value of 0.009 for the difference in proportions.</jats:p><jats:p><jats:bold>Conclusion</jats:bold> <jats:italic>FMR1</jats:italic> gray zone alleles are a significant risk factor for parkinsonism in females. These population data and occasional reports of FXTAS‐like or parkinsonian manifestations in carriers suggest possible mechanisms whereby the effects of these alleles synergize with the existing pathologies underpinning parkinsonism. © 2018 International Parkinson and Movement Disorder Society</jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"30153395","pmcid":"PMC6116531","openalex_id":null,"authors":[],"funders":[{"funder_name":"NICHD NIH HHS","grant_id":"R01 HD036071","title":null},{"funder_name":"CRC","grant_id":"","title":null}],"total_grants":2,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"bronze","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/mds.27420","host_type":"publisher"},{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fmds.27420","host_type":"publisher"},{"url":"https://movementdisorders.onlinelibrary.wiley.com/doi/pdf/10.1002/mds.27420","host_type":"publisher"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/6116531","host_type":"repository"}],"fields_of_study":[],"mesh_terms":["Humans","Parkinsonian Disorders","Genetic Predisposition to Disease","Risk Factors","Cohort Studies","DNA Mutational Analysis","Sex Factors","Trinucleotide Repeat Expansion","Gene Frequency","Genotype","Female","Fragile X Messenger Ribonucleoprotein 1"],"keywords":["Parkinson's Disease","Carrier Screening","Fmr1 Gene","Grey Zone Alleles","Increased Risk"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-17T17:36:09.621668Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}