{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:44:57Z","timestamp":1790253897970,"version":"4.1.0"},"reference-count":82,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2002,4,18]],"date-time":"2002-04-18T00:00:00Z","timestamp":1019088000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microscopy Res &amp;amp; Technique"],"published-print":{"date-parts":[[2002,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Fragile X syndrome (FraX) is one of the most prevalent genetic causes of mental retardation. FraX is associated with an unstable expansion of a polymorphism within the 5\u2032 untranslated region of the <jats:italic>FMR1<\/jats:italic> gene. The main consequence of this mutation is a reduction in the levels of the gene product (FMRP). FMRP is an RNA\u2010binding protein with multiple spliced variants (isoforms) and high levels of expression in a variety of tissues, including neurons. In the latter cells, it is localized not only to the perikaryon but also to dendrites and dendritic spines. FMRP belongs to a family of proteins that includes the Fragile X Related Proteins or FXRPs. FXRPs share high homology in their functional domains with FMRP, and also associate with mRNA and components of the protein synthesis apparatus. However, FXRPs do not have the same temporo\u2010spatial pattern of distribution (and other properties) of FMRP. Immunochemical assays have confirmed that a functionally uncompensated FMRP deficit is the essence of the FraX molecular phenotype. Here, we report our preliminary study on FXRPs levels in leukocytes from FraX males. By immunoblotting, we found that a marked reduction in FMRP levels is associated with a modest increase in FXR1P and no changes in FXR2P levels. The consequences of this reduced FMRP expression on protein synthesis, in other words, the identification of FMRP targets, can be studied by different molecular approaches including protein interaction and proteomics methods. By two\u2010dimensional gel electrophoresis, we showed that in FraX leukocytes there is a defect in acetylation that involves prominently the regulatory protein annexin\u20101. Extension of current studies of the molecular phenotype to more brain\u2010relevant tissue samples, a wider range of proteomics\u2010based methods, and correlative analyses of FMRP homologues and FMRP targets with multiple behavioral measures, will greatly expand our understanding of FraX pathogenesis and it will help to develop and monitor new therapeutic strategies. Microsc. Res. Tech. 57:135\u2013144, 2002. \u00a9 2002 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jemt.10066","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T19:45:33Z","timestamp":1030304733000},"page":"135-144","source":"Crossref","is-referenced-by-count":18,"title":["Molecular phenotype of Fragile X syndrome: FMRP, FXRPs, and protein targets"],"prefix":"10.1002","volume":"57","author":[{"given":"Walter E.","family":"Kaufmann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Cohen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong\u2010Tao","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Ho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2002,4,18]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19990101)82:1<25::AID-AJMG5>3.0.CO;2-Y"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0793-244"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1010747131386"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.13.2557"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.3313"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.103.2.545"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1999.9464"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.12.7925"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/6.9.1465"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0193-31"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0893-335"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/5.8.1083"},{"key":"e_1_2_1_14_1","first-page":"106","article-title":"Quantitative comparison of FMRI gene expression in normal and premutation alleles","volume":"56","author":"Feng Y","year":"1995","journal-title":"Am J Hum Genet"},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80012-X"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-05-01539.1997"},{"key":"e_1_2_1_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1996.tb00924.x"},{"key":"e_1_2_1_18_1","first-page":"47","article-title":"Beauty is skin deep: the fascinating biology of the epidermis and its appendages","volume":"94","author":"Fuchs E","year":"1998","journal-title":"Harvey Lect"},{"key":"e_1_2_1_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0892-341"},{"key":"e_1_2_1_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.141145998"},{"key":"e_1_2_1_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320510404"},{"key":"e_1_2_1_22_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.57.1.127"},{"key":"e_1_2_1_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.5.1927"},{"key":"e_1_2_1_24_1","first-page":"67","article-title":"Two new cases of FMR1 deletion associated with mental impairment","volume":"56","author":"Hirst M","year":"1995","journal-title":"Am J Hum Genet"},{"key":"e_1_2_1_25_1","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1600169"},{"key":"e_1_2_1_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4927(97)00019-X"},{"key":"e_1_2_1_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/10.10.981"},{"key":"e_1_2_1_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19990205)88:1<11::AID-AJMG3>3.0.CO;2-O"},{"key":"e_1_2_1_29_1","first-page":"454","article-title":"FMR Protein isoform quantitation: a complementary diagnostic assay for Fragile X syndrome","volume":"13","author":"Kaufmann WE","year":"1998","journal-title":"J Child Neurol"},{"key":"e_1_2_1_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19990402)83:4<286::AID-AJMG10>3.0.CO;2-H"},{"key":"e_1_2_1_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/10.10.992"},{"key":"e_1_2_1_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.14.1449"},{"key":"e_1_2_1_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/4.5.783"},{"key":"e_1_2_1_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0196-91"},{"key":"e_1_2_1_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/7.13.2121"},{"key":"e_1_2_1_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.6.1176"},{"key":"e_1_2_1_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.4.329"},{"key":"e_1_2_1_38_1","doi-asserted-by":"publisher","DOI":"10.1006\/cbir.2000.0629"},{"key":"e_1_2_1_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/29.11.2276"},{"key":"e_1_2_1_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/3.4.615"},{"key":"e_1_2_1_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/335726a0"},{"key":"e_1_2_1_42_1","first-page":"1252","article-title":"Familial transmission of the FMR1 CGG repeat","volume":"59","author":"Nolin SL","year":"1996","journal-title":"Am J Hum Genet"},{"key":"e_1_2_1_43_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.252.5009.1097"},{"key":"e_1_2_1_44_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-199511000-00001"},{"key":"e_1_2_1_45_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199705260-00016"},{"key":"e_1_2_1_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90125-I"},{"key":"e_1_2_1_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1195-331"},{"key":"e_1_2_1_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-2126(00)00093-9"},{"key":"e_1_2_1_49_1","first-page":"225","article-title":"A multicenter study on genotype\u2010phenotype correlations in the fragile X syndrome, using direct diagnosis with probe StB12.3: the first 2,253 cases","volume":"55","author":"Rousseau F","year":"1994","journal-title":"Am J Hum Genet"},{"key":"e_1_2_1_50_1","first-page":"1006","article-title":"Prevalence of carriers of premutation\u2010size alleles of the FMR1 gene an implications for the population genetics of the fragile X syndrome","volume":"57","author":"Rousseau F","year":"1995","journal-title":"Am J Hum Genet"},{"key":"e_1_2_1_51_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.151231598"},{"key":"e_1_2_1_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1522-2683(19990101)20:4\/5<984::AID-ELPS984>3.0.CO;2-R"},{"key":"e_1_2_1_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/1096-8628(200023)97:3<189::AID-AJMG1036>3.0.CO;2-J"},{"key":"e_1_2_1_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90420-U"},{"key":"e_1_2_1_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90232-1"},{"key":"e_1_2_1_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1995.tb07237.x"},{"key":"e_1_2_1_57_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.16.7.3825"},{"key":"e_1_2_1_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/1096-8628(20010915)103:1<81::AID-AJMG1505>3.0.CO;2-T"},{"key":"e_1_2_1_59_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.3405"},{"key":"e_1_2_1_60_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-10-03383.2001"},{"key":"e_1_2_1_61_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/5.6.809"},{"key":"e_1_2_1_62_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/6.8.1315"},{"key":"e_1_2_1_63_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.5.863"},{"key":"e_1_2_1_64_1","doi-asserted-by":"publisher","DOI":"10.1042\/0264-6021:3430517"},{"key":"e_1_2_1_65_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19990528)84:3<250::AID-AJMG17>3.0.CO;2-4"},{"key":"e_1_2_1_66_1","doi-asserted-by":"publisher","DOI":"10.1002\/1096-8628(200023)97:3<195::AID-AJMG1037>3.0.CO;2-R"},{"key":"e_1_2_1_67_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(20000313)91:2<144::AID-AJMG14>3.0.CO;2-V"},{"key":"e_1_2_1_68_1","doi-asserted-by":"publisher","DOI":"10.1002\/1096-8628(20001113)95:2<105::AID-AJMG3>3.0.CO;2-6"},{"key":"e_1_2_1_69_1","doi-asserted-by":"publisher","DOI":"10.1038\/363722a0"},{"key":"e_1_2_1_70_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/4.5.895"},{"key":"e_1_2_1_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90397-H"},{"key":"e_1_2_1_72_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/2.4.399"},{"key":"e_1_2_1_73_1","first-page":"222","article-title":"Expression of annexin and annexin\u2010mRNA in rat brain under influence of steroid drugs","volume":"70","author":"Voermans PH","year":"1997","journal-title":"Acta Neurochir(Wien)"},{"key":"e_1_2_1_74_1","doi-asserted-by":"publisher","DOI":"10.1007\/PL00000898"},{"key":"e_1_2_1_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(95)90979-6"},{"key":"e_1_2_1_76_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1996.1126"},{"key":"e_1_2_1_77_1","doi-asserted-by":"publisher","DOI":"10.1086\/302462"},{"key":"e_1_2_1_78_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004703-200008000-00004"},{"key":"e_1_2_1_79_1","first-page":"299","article-title":"A microdeletion of less than 250 kb, including the proximal part of the FMR\u2010I gene and the fragile\u2010X site, in a male with the clinical phenotype of fragile\u2010X syndrome","volume":"51","author":"W\u00f6hrle D","year":"1992","journal-title":"Am J Hum Genet"},{"key":"e_1_2_1_80_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02919405"},{"key":"e_1_2_1_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-3223(93)90051-E"},{"key":"e_1_2_1_82_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1995.tb00220.x"},{"key":"e_1_2_1_83_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19990528)84:3<268::AID-AJMG20>3.0.CO;2-#"}],"container-title":["Microscopy Research and Technique"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjemt.10066","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jemt.10066","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T13:51:56Z","timestamp":1760622716000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/jemt.10066"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,4,18]]},"references-count":82,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2002,5]]}},"alternative-id":["10.1002\/jemt.10066"],"URL":"https:\/\/doi.org\/10.1002\/jemt.10066","archive":["Portico"],"relation":{},"ISSN":["1059-910X","1097-0029"],"issn-type":[{"value":"1059-910X","type":"print"},{"value":"1097-0029","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,4,18]]}}}