{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T18:41:11Z","timestamp":1763059271385,"version":"3.44.0"},"reference-count":15,"publisher":"S. Karger AG","issue":"4","license":[{"start":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T00:00:00Z","timestamp":1732752000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T00:00:00Z","timestamp":1732752000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Mol Syndromol"],"abstract":"<jats:p>&lt;p&gt;Introduction: Blended phenotypes resulting from the contribution of two or more genetic variants to the disease of a patient pose a significant diagnostic challenge. Correlating between the phenotypes and the genotypes of the affected patients is difficult in these cases, especially in the absence of a large family segregating the condition. Case Presentation: We report a child born to consanguineous Syrian parents with a complex phenotype including a skeletal dysplasia, characterized by a small thorax and phalangeal shortening, as well as cardiac anomalies and sensorineural hearing loss. Molecular analysis identified the presence of three potentially disease-causing genetic variants. These include homozygous variants in the IHH and TTC12B genes, known to be associated with acrocapitofemoral dysplasia (OMIM# 607778) and a form of short-rib thoracic dysplasia (OMIM# 613819), respectively, in addition to a heterozygous variant in the COL11A1 gene, associated with dominant forms of skeletal dysplasia, such as Marshall (OMIM# 154780) and Stickler (OMIM# 608481) syndromes, and hearing loss (OMIM# 618533). Conclusion: We propose that the complex phenotype observed in the patient results from the contribution of l three of these variants. This case highlights some of the challenges encountered in the genetic counseling of families with rare genetic conditions. &lt;\/p&gt;<\/jats:p>","DOI":"10.1159\/000542345","type":"journal-article","created":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T12:00:52Z","timestamp":1732795252000},"page":"374-383","source":"Crossref","is-referenced-by-count":1,"title":["Co-Occurrence of Variants in 3 Genes in a Patient with Congenital Skeletal Dysplasia and Cardiac Anomalies: Diagnostic Challenge Posed by a Blended Phenotype"],"prefix":"10.1159","volume":"16","author":[{"given":"Pratibha","family":"Nair","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sami","family":"Bizzari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cybel","family":"Mehawej","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6257-6609","authenticated-orcid":false,"given":"Eliane","family":"Chouery","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Perla","family":"Audi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Corbani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rima","family":"Korban","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5569-5167","authenticated-orcid":false,"given":"Daniel","family":"Mahfoud","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Superti-Furga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stepahny","family":"El-Hayek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0714-2469","authenticated-orcid":false,"given":"Andre","family":"Megarbane","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2024,11,28]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1516767"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-019-0477-2"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.40.1.42"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.40.3.201"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1086\/374318"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1186\/s40246-022-00421-z"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1038\/ng.756"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1038\/hgv.2016.3"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-40909-3"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awad111"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.3390\/genes13071275"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1159\/000506530"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1002\/mds.29147"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2015.285"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-021-00933-7"}],"container-title":["Molecular Syndromology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/karger.com\/msy\/article-pdf\/doi\/10.1159\/000542345\/4306069\/000542345.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/karger.com\/article-pdf\/doi\/10.1159\/000542345","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T16:04:33Z","timestamp":1758297873000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000542345"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,28]]},"references-count":15,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,8,5]]},"published-print":{"date-parts":[[2025,8,6]]}},"URL":"https:\/\/doi.org\/10.1159\/000542345","archive":["Portico"],"relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.6084\/m9.figshare.27330183","asserted-by":"subject"}]},"ISSN":["1661-8769","1661-8777"],"issn-type":[{"type":"print","value":"1661-8769"},{"type":"electronic","value":"1661-8777"}],"subject":[],"published":{"date-parts":[[2024,11,28]]}}}