{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:46:29Z","timestamp":1787312789205,"version":"build-2736575974"},"reference-count":19,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,2,10]],"date-time":"2024-02-10T00:00:00Z","timestamp":1707523200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"La Direction de la Recherche Clinique et de l\u2019Innovation (DRCI), CHU Clermont-Ferrand, France"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Skeletal dysplasia, also called osteochondrodysplasia, is a category of disorders affecting bone development and children\u2019s growth. Up to 552 genes, including fibroblast growth factor receptor 3 (FGFR3), have been implicated by pathogenic variations in its genesis. Frequently identified causal mutations in osteochondrodysplasia arise in the coding sequences of the FGFR3 gene: c.1138G&gt;A and c.1138G&gt;C in achondroplasia and c.1620C&gt;A and c.1620C&gt;G in hypochondroplasia. However, in some cases, the diagnostic investigations undertaken thus far have failed to identify the causal anomaly, which strengthens the relevance of the diagnostic strategies being further refined. We observed a Caucasian adult with clinical and radiographic features of achondroplasia, with no common pathogenic variant. Exome sequencing detected an FGFR3(NM_000142.4):c.1075+95C&gt;G heterozygous intronic variation. In vitro studies showed that this variant results in the aberrant exonization of a 90-nucleotide 5\u2032 segment of intron 8, resulting in the substitution of the alanine (Ala359) for a glycine (Gly) and the in-frame insertion of 30 amino acids. This change may alter FGFR3\u2019s function. Our report provides the first clinical description of an adult carrying this variant, which completes the phenotype description previously provided in children and confirms the recurrence, the autosomal-dominant pathogenicity, and the diagnostic relevance of this FGFR3 intronic variant. We support its inclusion in routinely used diagnostic tests for osteochondrodysplasia. This may increase the detection rate of causal variants and therefore could have a positive impact on patient management. Finally, FGFR3 alteration via non-coding sequence exonization should be considered a recurrent disease mechanism to be taken into account for new drug design and clinical trial strategies.<\/jats:p>","DOI":"10.3390\/genes15020225","type":"journal-article","created":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T04:47:45Z","timestamp":1707713265000},"page":"225","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Relevance of Extending FGFR3 Gene Analysis in Osteochondrodysplasia to Non-Coding Sequences: A Case Report"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1142-8788","authenticated-orcid":false,"given":"Zangb\u00e9wend\u00e9 Guy","family":"Ouedraogo","sequence":"first","affiliation":[{"name":"Service de Biochimie et G\u00e9n\u00e9tique Mol\u00e9culaire, CHU Gabriel Montpied, CHU Clermont-Ferrand, 63000 Clermont-Ferrand, France"},{"name":"Universit\u00e9 Clermont Auvergne, CNRS, Inserm, iGReD, 63001 Clermont-Ferrand, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Janel","sequence":"additional","affiliation":[{"name":"Service de Biochimie et G\u00e9n\u00e9tique Mol\u00e9culaire, CHU Gabriel Montpied, CHU Clermont-Ferrand, 63000 Clermont-Ferrand, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Janin","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Fonctionnelle Cardiog\u00e9n\u00e9tique, Mol\u00e9culaire, Centre de Biologie et Pathologie Est, Hospices Civils de Lyon, 69677 Bron, France"},{"name":"CNRS UMR5261, INSERM U1315, Pathophysiology and Genetics of Neuron and Muscle, Institut Neuromyog\u00e8ne, Universit\u00e9 Claude Bernard Lyon 1, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6127-0694","authenticated-orcid":false,"given":"Gilles","family":"Millat","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Fonctionnelle Cardiog\u00e9n\u00e9tique, Mol\u00e9culaire, Centre de Biologie et Pathologie Est, Hospices Civils de Lyon, 69677 Bron, France"},{"name":"CNRS UMR5261, INSERM U1315, Pathophysiology and Genetics of Neuron and Muscle, Institut Neuromyog\u00e8ne, Universit\u00e9 Claude Bernard Lyon 1, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Langlais","sequence":"additional","affiliation":[{"name":"Service de Biochimie et G\u00e9n\u00e9tique Mol\u00e9culaire, CHU Gabriel Montpied, CHU Clermont-Ferrand, 63000 Clermont-Ferrand, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e9n\u00e9dicte","family":"Pontier","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale, CHU Estaing, CHU Clermont-Ferrand, 63100 Clermont-Ferrand, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Biard","sequence":"additional","affiliation":[{"name":"Service de Radiologie P\u00e9diatrique, CHU Estaing, CHU Clermont-Ferrand, 63100 Clermont-Ferrand, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathis","family":"Lepage","sequence":"additional","affiliation":[{"name":"Service de Biochimie et G\u00e9n\u00e9tique Mol\u00e9culaire, CHU Gabriel Montpied, CHU Clermont-Ferrand, 63000 Clermont-Ferrand, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Francannet","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale, CHU Estaing, CHU Clermont-Ferrand, 63100 Clermont-Ferrand, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanny","family":"Laffargue","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale, CHU Estaing, CHU Clermont-Ferrand, 63100 Clermont-Ferrand, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1779-5247","authenticated-orcid":false,"given":"Isabelle","family":"Creveaux","sequence":"additional","affiliation":[{"name":"Service de Biochimie et G\u00e9n\u00e9tique Mol\u00e9culaire, CHU Gabriel Montpied, CHU Clermont-Ferrand, 63000 Clermont-Ferrand, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"689","DOI":"10.47162\/RJME.62.3.05","article-title":"Changes in skeletal dysplasia nosology","volume":"62","author":"Mirodot","year":"2021","journal-title":"Rom. 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