{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T12:21:14Z","timestamp":1761740474368,"version":"build-2065373602"},"reference-count":17,"publisher":"LIDSEN Publishing Inc","issue":"04","license":[{"start":{"date-parts":[[2021,10,29]],"date-time":"2021-10-29T00:00:00Z","timestamp":1635465600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["OBM Genet"],"accepted":{"date-parts":[[2021,10,17]]},"published-print":{"date-parts":[[2021,10,29]]},"abstract":"<jats:p>The FRAXE section of the FMR2 gene, located on the X chromosome, contains varying numbers of trinucleotide repeats; boys with over 200 repeats tend to have mild cognitive impairments, though this is rare. Little is known, however, concerning the phenotypes of individuals with smaller numbers of repeats. Here we answer the research question as to whether the health of ancestors of boys from whom the relevant X chromosome was inherited differed in any way according to the number of FRAXE repeats. Numbers of FRAXE repeats in 5057 boys from the Avon Longitudinal Study of Parents and Children (ALSPAC) were assessed. The distribution was bimodal, with the second smaller distribution starting at 22 repeats. We tested whether possession of 22+ repeats was associated with differences in the health of mothers (who share the X chromosome) and maternal grandmothers (half of whom share it). Female ancestors of boys with &amp;gt;21 repeats compared with &amp;lt;22 showed that maternal grandmothers (MGM) and mothers (M) had an increased risk of diabetes: MGM Type I odds ratio (OR) 2.40 [95%CI: 1.07,5.38]; MGM Type II OR 1.61 [0.96,2.70]; M OR 1.95 [0.96,3.94] using self-reported questionnaire measures. These results were confirmed from maternal medical records which revealed an increased level of diabetes [OR 2.40 (1.16,4.96)] and an increased risk of repeated glycosuria during pregnancy [OR 1.60 (1.08,2.36)]. We tested numbers of FRAXA repeats and showed no such associations, indicating that the findings were not associated with triploid repeats in general. If these findings are replicated elsewhere, there are at least three possible interpretations: (i) maternal diabetes\/prediabetes results in an increased number of FRAXE repeats; (ii) women with high numbers of FRAXE repeats are at increased risk of diabetes; or (iii) some common factor, e.g. genomic instability, results in both diabetes and increased repeats.<\/jats:p>","DOI":"10.21926\/obm.genet.2104141","type":"journal-article","created":{"date-parts":[[2021,10,29]],"date-time":"2021-10-29T04:31:35Z","timestamp":1635481895000},"page":"1-16","update-policy":"https:\/\/doi.org\/10.21926\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Unexpected Associations between the Number of FRAXE Repeats in Boys and Evidence of Diabetes in Their Mothers and Maternal Grandmothers"],"prefix":"10.21926","volume":"05","author":[{"given":"Jean","family":"Golding","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosie","family":"Clark","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven","family":"Gregory","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Genette","family":"Ellis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Suderman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasmin","family":"Iles-Caven","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcus E.","family":"Pembrey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"9387","published-online":{"date-parts":[[2021,10,29]]},"reference":[{"key":"ref=1","doi-asserted-by":"crossref","unstructured":"Knight SJ, Flannery AV, Hirst MC, Campbell L, Christodoulou Z, Phelps SR, et al. Trinucleotide repeat amplification and hypermethylation of a CpG island in FRAXE mental retardation. Cell. 1993; 74: 127-134.","DOI":"10.1016\/0092-8674(93)90300-F"},{"key":"ref=2","doi-asserted-by":"crossref","unstructured":"Murray A, Ennis S, Youings SA, Sharrock AJ, Lewis C, Pound MC, et al. Stability and haplotype analysis of the FRAXE region. Eur J Hum Genet. 2000; 8: 583-589.","DOI":"10.1038\/sj.ejhg.5200504"},{"key":"ref=3","doi-asserted-by":"crossref","unstructured":"Clark R, Gregory S, Ring S, Jacobs P, Ennis S, Murray A, et al. The FRAXA and FRAXE allele repeat size of boys from the Avon Longitudinal Study of Parents and Children (ALSPAC). Wellcome Open Res. 2019; 4: 116.","DOI":"10.12688\/wellcomeopenres.15342.1"},{"key":"ref=4","doi-asserted-by":"crossref","unstructured":"Youings SA, Murray A, Dennis N, Ennis S, Lewis C, McKechnie N, et al. FRAXA and FRAXE: The results of a five year survey. J Med Genet. 2000; 37: 415-421.","DOI":"10.1136\/jmg.37.6.415"},{"key":"ref=5","doi-asserted-by":"crossref","unstructured":"Dennis NR, Curtis G, Macpherson JN, Jacobs PA. Two families with Xq27. 3 fragility, no detectable insert in the FMR-1 gene, mild mental impairment, and absence of the Martin-Bell phenotype. Am J Med Genet. 1992; 43: 232-236.","DOI":"10.1002\/ajmg.1320430137"},{"key":"ref=6","unstructured":"Hamel BC, Smits AP, de Graaff E, Smeets DF, Schoute F, Eussen BH, et al. Segregation of FRAXE in a large family: Clinical, psychometric, cytogenetic, and molecular data. Am J Hum Genet. 1994; 55: 923-931."},{"key":"ref=7","doi-asserted-by":"crossref","unstructured":"Mulley JC, Yu S, Loesch DZ, Hay DA, Donnelly A, Gedeon AK, et al. FRAXE and mental retardation. J Med Genet. 1995; 32: 162-169.","DOI":"10.1136\/jmg.32.3.162"},{"key":"ref=8","unstructured":"Knight SJ, Ritchie RJ, Chakrabarti L, Cross G, Taylor GR, Mueller RF, et al. A study of FRAXE in mentally retarded individuals referred for fragile X syndrome (FRAXA) testing in the United Kingdom. Am J Hum Genet. 1996; 58: 906-913."},{"key":"ref=9","doi-asserted-by":"crossref","unstructured":"Barnicoat AJ, Wang Q, Turk J, Green E, Mathew CG, Flynn G, et al. Clinical, cytogenetic, and molecular analysis of three families with FRAXE. J Med Genet. 1997; 34: 13-17.","DOI":"10.1136\/jmg.34.1.13"},{"key":"ref=10","doi-asserted-by":"crossref","unstructured":"Musumeci SA, Ferri R, Scuderi C, Bosco P, Elia M. Seizures and epileptiform EEG abnormalities in FRAXE syndrome. Clin Neurophysiol. 2001; 112: 1954-1955.","DOI":"10.1016\/S1388-2457(01)00621-6"},{"key":"ref=11","doi-asserted-by":"crossref","unstructured":"Boyd A, Golding J, Macleod J, Lawlor DA, Fraser A, Henderson J, et al. Cohort profile: The \u2018children of the 90s\u2019-the index offspring of the Avon Longitudinal Study of Parents and Children. Int J Epidemiol. 2013; 42: 111-127.","DOI":"10.1093\/ije\/dys064"},{"key":"ref=12","doi-asserted-by":"crossref","unstructured":"Fraser A, Macdonald-Wallis C, Tilling K, Boyd A, Golding J, Davey Smith G, et al. Cohort profile: The Avon Longitudinal Study of parents and Children: ALSPAC mothers cohort. Int J Epidemiol. 2013; 42: 97-110.","DOI":"10.1093\/ije\/dys066"},{"key":"ref=13","doi-asserted-by":"crossref","unstructured":"Golding J, Pembrey M, Jones R. ALSPAC Study Team. ALSPAC-the Avon Longitudinal Study of Parents and Children. Paediatr Perinat Epidemiol. 2001; 15: 74-87.","DOI":"10.1046\/j.1365-3016.2001.00325.x"},{"key":"ref=14","doi-asserted-by":"crossref","unstructured":"Ennis S, Murray A, Youings S, Brightwell G, Herrick D, Ring S, et al. An investigation of FRAXA intermediate allele phenotype in a longitudinal sample. Ann Hum Genet. 2006; 70: 170-180.","DOI":"10.1111\/j.1529-8817.2005.00220.x"},{"key":"ref=15","doi-asserted-by":"crossref","unstructured":"Jones RW, Ring S, Tyfield L, Hamvas R, Simmons H, Pembrey M, et al. A new human genetic resource: A DNA bank established as part of the Avon longitudinal study of pregnancy and childhood (ALSPAC). Eur J Hum Genet. 2000; 8: 653-660.","DOI":"10.1038\/sj.ejhg.5200502"},{"key":"ref=16","doi-asserted-by":"crossref","unstructured":"Murray A, Youings S, Dennis N, Latsky L, Linehan P, McKechnie N, et al. Population screening at the FRAXA and FRAXE loci: Molecular analyses of boys with learning difficulties and their mothers. Hum Mol Genet. 1996; 5: 727-735.","DOI":"10.1093\/hmg\/5.6.727"},{"key":"ref=17","doi-asserted-by":"crossref","unstructured":"Birmingham K. Pioneering ethics in a longitudinal study. Bristol: Policy Press; 2018. pp.136.","DOI":"10.1332\/9781447340423"}],"container-title":["OBM Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.lidsen.com\/journals\/genetics\/genetics-05-04-141\/obm.genet.2104141.xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.lidsen.com\/journals\/genetics\/genetics-05-04-141","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T06:39:39Z","timestamp":1761719979000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.lidsen.com\/journals\/genetics\/genetics-05-04-141"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,29]]},"references-count":17,"journal-issue":{"issue":"04","published-online":{"date-parts":[[2021]]},"published-print":{"date-parts":[[2021]]}},"URL":"https:\/\/doi.org\/10.21926\/obm.genet.2104141","relation":{},"ISSN":["2577-5790"],"issn-type":[{"type":"electronic","value":"2577-5790"}],"subject":[],"published":{"date-parts":[[2021,10,29]]}}}