{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T08:20:48Z","timestamp":1767860448571,"version":"3.49.0"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T00:00:00Z","timestamp":1663113600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82000745"],"award-info":[{"award-number":["82000745"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The <jats:italic>PTPN11<\/jats:italic> gene, located at 12q24. 13, encodes protein tyrosine phosphatase 2C. Mutations in the <jats:italic>PTPN11<\/jats:italic> gene can lead to various phenotypes, including Noonan syndrome and LEOPARD syndrome. The <jats:italic>SEC24D<\/jats:italic> gene is located at 4q26 and encodes a component of the COPII complex, and is closely related to endoplasmic reticulum protein transport. Mutations in <jats:italic>SEC24D<\/jats:italic> can lead to Cole-Carpenter syndrome-2. To date, dual mutations in these two genes have not been reported in the literature.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We report a patient with short stature and osteogenesis imperfecta as the primary clinical manifestation. Other clinical features were peculiar facial features, deafness, and a history of recurrent fractures. Whole exome sequencing was performed on this patient.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>After whole-exome sequencing, three mutations in two genes were identified that induced protein alterations associated with the patient's phenotype. One was a de novo variant c.1403C&amp;gt;T (p.Thr468Met) on exon 12 of the <jats:italic>PTPN11<\/jats:italic> gene, and the other was a compound heterozygous mutation in the <jats:italic>SEC24D<\/jats:italic> gene, a novel variant c.2609_2610delGA (p.Arg870Thrfs<jats:sup>*<\/jats:sup>10) on exon 20 and a reported variant c.938G&amp;gt;A (p.Arg313His) on exon 8.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Concurrent mutations in <jats:italic>PTPN11<\/jats:italic> and <jats:italic>SEC24D<\/jats:italic> induced a phenotype that was significantly different from individual mutations in either <jats:italic>PTPN11<\/jats:italic> or <jats:italic>SEC24D<\/jats:italic> gene. Personalized genetic analysis and interpretation could help us understand the patient's etiology and hence develop treatments and improve the prognosis of these patients.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fped.2022.973920","type":"journal-article","created":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T06:30:34Z","timestamp":1663137034000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Case report: Clinical manifestations and genotype analysis of a child with PTPN11 and SEC24D 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