{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T17:41:35Z","timestamp":1784137295502,"version":"3.55.0"},"reference-count":4,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T00:00:00Z","timestamp":1746662400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["FIS PI20\/01053"],"award-info":[{"award-number":["FIS PI20\/01053"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PMP21\/00063"],"award-info":[{"award-number":["PMP21\/00063"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PMP22\/00049"],"award-info":[{"award-number":["PMP22\/00049"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2025,8]]},"abstract":"ABSTRACT<\/jats:title>\n \n We present a 28\u2010year\u2010old Spanish female with a\n de novo<\/jats:italic>\n heterozygous variant in\n FMR1<\/jats:italic>\n (NM_002024.6:c.1061_1062delAA), p.(Lys354Thrfs*15) detected by whole\u2010exome sequencing and confirmed by Sanger sequencing from cDNA. She was born full\u2010term with neonatal jaundice requiring phototherapy. At age 11, she exhibited weight and head circumference\u2009>\u200997th percentile, global developmental delay, mild ID (IQ: 71), and hyperactivity.\n FMR1<\/jats:italic>\n CGG analysis was normal. NGS panel of over 200 OGS\u2010related genes found no pathogenic variants. By age 28, she presented with macrocephaly, coarse facial features, mild joint hypermobility, left talo\u2010valgus, a port\u2010wine stain, a caf\u00e9\u2010au\u2010lait spot, and a piezogenic papule. Herein, we describe a clinical and molecular report of the second FXS female patient due to a heterozygous point variant. This study was approved by the ethical committee of Hospital Universitario La Paz (CEIm PI\u2010446), and informed consent was obtained from the patient and her parents.\n <\/jats:p>","DOI":"10.1111\/cge.14761","type":"journal-article","created":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T20:08:15Z","timestamp":1746734895000},"page":"224-226","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Identification of a De Novo Heterozygous Frameshift Variant in\n FMR1<\/scp>\n in a Female With Fragile X Syndrome"],"prefix":"10.1111","volume":"108","author":[{"given":"Alejandro","family":"Parra","sequence":"first","affiliation":[{"name":"CIBERER, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras Madrid Spain"},{"name":"INGEMM\u2010Idipaz, Institute of Medical and Molecular Genetics Madrid Spain"},{"name":"ITHACA, European Reference Network, Hospital Universitario La Paz Madrid Spain"},{"name":"Escuela del Doctorado, Universidad Aut\u00f3noma de Madrid Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan A.","family":"Jimenez\u2010Estrada","sequence":"additional","affiliation":[{"name":"CIBERER, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras Madrid Spain"},{"name":"INGEMM\u2010Idipaz, Institute of Medical and Molecular Genetics Madrid Spain"},{"name":"ITHACA, European Reference Network, Hospital Universitario La Paz Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"V\u00e1squez\u2010Amell","sequence":"additional","affiliation":[{"name":"INGEMM\u2010Idipaz, Institute of Medical and Molecular Genetics Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Cazalla","sequence":"additional","affiliation":[{"name":"CIBERER, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras Madrid Spain"},{"name":"INGEMM\u2010Idipaz, Institute of Medical and Molecular Genetics Madrid Spain"},{"name":"ITHACA, European Reference Network, Hospital Universitario La Paz Madrid Spain"},{"name":"Escuela del Doctorado, Universidad Aut\u00f3noma de Madrid Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Rodr\u00edguez\u2010Can\u00f3","sequence":"additional","affiliation":[{"name":"CIBERER, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras Madrid Spain"},{"name":"INGEMM\u2010Idipaz, Institute of Medical and Molecular Genetics Madrid Spain"},{"name":"ITHACA, European Reference Network, Hospital Universitario La Paz Madrid Spain"},{"name":"Escuela del Doctorado, Universidad Aut\u00f3noma de Madrid Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Gallego\u2010Zazo","sequence":"additional","affiliation":[{"name":"CIBERER, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras Madrid Spain"},{"name":"INGEMM\u2010Idipaz, Institute of Medical and Molecular Genetics Madrid Spain"},{"name":"ITHACA, European Reference Network, Hospital Universitario La Paz Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Miranda","sequence":"additional","affiliation":[{"name":"CIBERER, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras Madrid Spain"},{"name":"INGEMM\u2010Idipaz, Institute of Medical and Molecular Genetics Madrid Spain"},{"name":"ITHACA, European Reference Network, Hospital Universitario La Paz Madrid Spain"},{"name":"Escuela del Doctorado, Universidad Aut\u00f3noma de Madrid Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f3nica","family":"Mora\u2010G\u00f3mez","sequence":"additional","affiliation":[{"name":"CIBERER, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras Madrid Spain"},{"name":"INGEMM\u2010Idipaz, Institute of Medical and Molecular Genetics Madrid Spain"},{"name":"ITHACA, European Reference Network, Hospital Universitario La Paz Madrid Spain"},{"name":"Escuela del Doctorado, Universidad Aut\u00f3noma de Madrid Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Vallesp\u00edn","sequence":"additional","affiliation":[{"name":"CIBERER, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras Madrid Spain"},{"name":"INGEMM\u2010Idipaz, Institute of Medical and Molecular Genetics Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roc\u00edo","family":"Mena","sequence":"additional","affiliation":[{"name":"CIBERER, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras Madrid Spain"},{"name":"INGEMM\u2010Idipaz, Institute of Medical and Molecular Genetics Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1791-4936","authenticated-orcid":false,"given":"Luis","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"CIBERER, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras Madrid Spain"},{"name":"INGEMM\u2010Idipaz, Institute of Medical and Molecular Genetics Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Silv\u00e1n","sequence":"additional","affiliation":[{"name":"INGEMM\u2010Idipaz, Institute of Medical and Molecular Genetics Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Arias","sequence":"additional","affiliation":[{"name":"CIBERER, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras Madrid Spain"},{"name":"INGEMM\u2010Idipaz, Institute of Medical and Molecular Genetics Madrid Spain"},{"name":"ITHACA, European Reference Network, Hospital Universitario La Paz Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Dominguez\u2010Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Instituto Murciano de Investigaci\u00f3n Biosanitaria (IMIB) Murcia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Encarna","family":"Guill\u00e9n\u2010Navarro","sequence":"additional","affiliation":[{"name":"CIBERER, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras Madrid Spain"},{"name":"Instituto Murciano de Investigaci\u00f3n Biosanitaria (IMIB) Murcia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juli\u00e1n","family":"Nevado","sequence":"additional","affiliation":[{"name":"CIBERER, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras Madrid Spain"},{"name":"INGEMM\u2010Idipaz, Institute of Medical and Molecular Genetics Madrid Spain"},{"name":"ITHACA, European Reference Network, 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Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6324-4825","authenticated-orcid":false,"given":"Pablo","family":"Lapunzina","sequence":"additional","affiliation":[{"name":"CIBERER, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras Madrid Spain"},{"name":"INGEMM\u2010Idipaz, Institute of Medical and Molecular Genetics Madrid Spain"},{"name":"ITHACA, European Reference Network, Hospital Universitario La Paz Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,8]]},"reference":[{"key":"e_1_2_4_2_1","doi-asserted-by":"publisher","DOI":"10.3233\/TRD-180028"},{"key":"e_1_2_4_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2016.20428176767"},{"key":"e_1_2_4_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36511"},{"key":"e_1_2_4_5_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201404576"}],"container-title":["Clinical 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