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Only 20% of female premutation carriers develop early ovulatory dysfunction, the reason for this incomplete penetrance is unknown. This study validated the mathematical model in premutation alleles, after assigning each allele a score representing allelic complexity. Subsequently, <jats:italic>allelic scores<\/jats:italic> were used to investigate the impact of allele complexity on age at amenorrhea for 58 premutation cases (116 alleles) previously published.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>The <jats:italic>allelic score<\/jats:italic> was determined using a formula previously described by our group. The impact of each <jats:italic>allelic score<\/jats:italic> on age at amenorrhea was analyzed using Pearson\u2019s test and a contour plot generated to visualize the effect.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Correlation of <jats:italic>allelic score<\/jats:italic> revealed two distinct complexity behaviors in premutation alleles. No significant correlation was observed between the <jats:italic>allelic score<\/jats:italic> of premutation alleles and age at amenorrhea. The same lack of significant correlation was observed regarding normal-sized alleles, despite a nearly significant trend.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Our results suggest that the use of <jats:italic>allelic scores<\/jats:italic> combination have the potential to explain female infertility, namely the development of FXPOI, or ovarian dysfunction, despite the lack of correlation with age at amenorrhea. Such a finding is of great clinical significance for early identification of females at risk of ovulatory dysfunction, enhancement of fertility preservation techniques, and increasing the probability for a successful pregnancy in females with premutations. Additional investigation is necessary to validate this hypothesis.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12958-024-01227-5","type":"journal-article","created":{"date-parts":[[2024,6,21]],"date-time":"2024-06-21T08:02:02Z","timestamp":1718956922000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["FMR1 allelic complexity in premutation carriers provides no evidence for a correlation with age at amenorrhea"],"prefix":"10.1186","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4698-962X","authenticated-orcid":false,"given":"B\u00e1rbara","family":"Rodrigues","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5855-1863","authenticated-orcid":false,"given":"Vanessa","family":"Sousa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2399-6176","authenticated-orcid":false,"given":"Carolyn M.","family":"Yrigollen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6388-9180","authenticated-orcid":false,"given":"Flora","family":"Tassone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5574-837X","authenticated-orcid":false,"given":"Olatz","family":"Villate","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0963-036X","authenticated-orcid":false,"given":"Emily G.","family":"Allen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Glicksman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Tortora","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5209-289X","authenticated-orcid":false,"given":"Sarah L.","family":"Nolin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7089-2508","authenticated-orcid":false,"given":"Ant\u00f3nio J. 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Participants of set 1 the informed consent approved by the clinical ethical committee of Cruces Hospital was obtained in all cases prior to genetic testing. Protocols and consent forms of participants in set 2 were conducted in concordance with the Belmont Report and approved by the Institutional Review Board at Emory University, and written informed consent was obtained from all subjects (IRB00045808). Participants of the set 3 were recruited through the Fragile X Research and Treatment Center at the MIND Institute \u2013 University of California Davis, USA. Whole blood was collected according to protocols approved by the Institutional Review Board at the University of California, Davis, and informed consent was obtained from all patients. This research was approved from the Ethics Committee of the Unidade Local de Sa\u00fade de Santo Ant\u00f3nio (2020.119 \/097-DEFI\/099-CE) as part of B. 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