{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T06:34:57Z","timestamp":1776407697672,"version":"3.51.2"},"reference-count":31,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,11,27]],"date-time":"2021-11-27T00:00:00Z","timestamp":1637971200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MIUR-University","award":["Grant D3.2-2017"],"award-info":[{"award-number":["Grant D3.2-2017"]}]},{"name":"MIUR-University","award":["Grant D.1-2020"],"award-info":[{"award-number":["Grant D.1-2020"]}]},{"name":"PRIN","award":["Prot. 201789LFKB"],"award-info":[{"award-number":["Prot. 201789LFKB"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Fragile X syndrome (FXS) is the most common form of inherited intellectual disability and autism caused by the instability of a CGG trinucleotide repeat in exon 1 of the FMR1 gene. The co-occurrence of FXS with other genetic disorders has only been occasionally reported. Here, we describe three independent cases of FXS co-segregation with three different genetic conditions, consisting of Duchenne muscular dystrophy (DMD), PPP2R5D--related neurodevelopmental disorder, and 2p25.3 deletion. The co-occurrence of DMD and FXS has been reported only once in a young boy, while in an independent family two affected boys were described, the elder diagnosed with FXS and the younger with DMD. This represents the second case in which both conditions coexist in a 5-year-old boy, inherited from his heterozygous mother. The next double diagnosis had never been reported before: through exome sequencing, a girl with FXS who was of 7 years of age with macrocephaly and severe psychomotor delay was found to carry a de novo variant in the PPP2R5D gene. Finally, a maternally inherited 2p25.3 deletion associated with a decreased level of the MYT1L transcript, only in the patient, was observed in a 33-year-old FXS male with severe seizures compared to his mother and two sex- and age-matched controls. All of these patients represent very rare instances of genetic conditions with clinical features that can be modified by FXS and vice versa.<\/jats:p>","DOI":"10.3390\/genes12121909","type":"journal-article","created":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T05:23:02Z","timestamp":1638163382000},"page":"1909","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Co-Occurrence of Fragile X Syndrome with a Second Genetic Condition: Three Independent Cases of Double Diagnosis"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4707-2242","authenticated-orcid":false,"given":"Elisabetta","family":"Tabolacci","sequence":"first","affiliation":[{"name":"Sezione di Medicina Genomica, Dipartimento Universitario Scienze della Vita e Sanit\u00e0 Pubblica, Universit\u00e0 Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Grazia","family":"Pomponi","sequence":"additional","affiliation":[{"name":"UOC Genetica Medica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Remondini","sequence":"additional","affiliation":[{"name":"UOC Genetica Medica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta","family":"Pietrobono","sequence":"additional","affiliation":[{"name":"UOC Genetica Medica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Orteschi","sequence":"additional","affiliation":[{"name":"UOC Genetica Medica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veronica","family":"Nobile","sequence":"additional","affiliation":[{"name":"Sezione di Medicina Genomica, Dipartimento Universitario Scienze della Vita e Sanit\u00e0 Pubblica, Universit\u00e0 Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cecilia","family":"Pucci","sequence":"additional","affiliation":[{"name":"Sezione di Medicina Genomica, Dipartimento Universitario Scienze della Vita e Sanit\u00e0 Pubblica, Universit\u00e0 Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisa","family":"Musto","sequence":"additional","affiliation":[{"name":"Sezione di Neuropsichiatria Infantile, Dipartimento Universitario Scienze della Vita e Sanit\u00e0 Pubblica, Facolt\u00e0 di Medicina e Chirurgia, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Unit\u00e0 di Neuropsichiatria Infantile, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marika","family":"Pane","sequence":"additional","affiliation":[{"name":"Sezione di Neuropsichiatria Infantile, Dipartimento Universitario Scienze della Vita e Sanit\u00e0 Pubblica, Facolt\u00e0 di Medicina e Chirurgia, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Unit\u00e0 di Neuropsichiatria Infantile, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eugenio M.","family":"Mercuri","sequence":"additional","affiliation":[{"name":"Sezione di Neuropsichiatria Infantile, Dipartimento Universitario Scienze della Vita e Sanit\u00e0 Pubblica, Facolt\u00e0 di Medicina e Chirurgia, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Unit\u00e0 di Neuropsichiatria Infantile, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Neri","sequence":"additional","affiliation":[{"name":"Sezione di Medicina Genomica, Dipartimento Universitario Scienze della Vita e Sanit\u00e0 Pubblica, Universit\u00e0 Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"},{"name":"JC Self Research Institute, Greenwood Genetic Center, Greenwood, SC 29646, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maurizio","family":"Genuardi","sequence":"additional","affiliation":[{"name":"Sezione di Medicina Genomica, Dipartimento Universitario Scienze della Vita e Sanit\u00e0 Pubblica, Universit\u00e0 Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"},{"name":"UOC Genetica Medica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5104-1521","authenticated-orcid":false,"given":"Pietro","family":"Chiurazzi","sequence":"additional","affiliation":[{"name":"Sezione di Medicina Genomica, Dipartimento Universitario Scienze della Vita e Sanit\u00e0 Pubblica, Universit\u00e0 Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"},{"name":"UOC Genetica Medica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4871-9519","authenticated-orcid":false,"given":"Marcella","family":"Zollino","sequence":"additional","affiliation":[{"name":"Sezione di Medicina Genomica, Dipartimento Universitario Scienze della Vita e Sanit\u00e0 Pubblica, Universit\u00e0 Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"},{"name":"UOC Genetica Medica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1002\/ajmg.a.36511","article-title":"Epidemiology of fragile X syndrome: A systematic review and meta-analysis","volume":"164","author":"Hunter","year":"2014","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.ajhg.2009.09.007","article-title":"Incidence of fragile X syndrome by newborn screening for methylated FMR1 DNA","volume":"85","author":"Coffee","year":"2009","journal-title":"Am. J. Hum. 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