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In the present study, a detailed phenotypic analysis performed for a total of five patients with Takenouchi-Kosaki syndrome revealed that intellectual disability, macrothrombocytopenia, camptodactyly, structural brain abnormalities with sensorineural deafness, hypothyroidism, and frequent infections comprise the cardinal features of this condition. A morphologic analysis of platelets derived from three affected individuals was performed using electron microscopy. The platelets of the three patients were large and spherical in shape. Furthermore, platelet \u03b1-granules were decreased, while vacuoles were increased. We further performed a functional analysis of p.Tyr64Cys in <jats:italic>CDC42<\/jats:italic> through CRISPR\/Cas9-mediated gene editing in a <jats:italic>Caenorhabditis elegans<\/jats:italic> model. This functional analysis suggested that the mutant allele has hypomorphic effects. Takenouchi-Kosaki syndrome is clinically recognizable by the combined phenotype of intellectual disability, macrothrombocytopenia, camptodactyly, structural brain abnormalities with sensorineural deafness, hypothyroidism, and frequent infections as well as the identification of a heterozygous <jats:italic>de novo<\/jats:italic> mutation in <jats:italic>CDC42<\/jats:italic>, i.e., p.Tyr64Cys.<\/jats:p>","DOI":"10.1038\/s41598-019-40988-7","type":"journal-article","created":{"date-parts":[[2019,3,14]],"date-time":"2019-03-14T12:06:06Z","timestamp":1552565166000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Pathogenetic basis of Takenouchi-Kosaki syndrome: Electron microscopy study using platelets in patients and functional studies in a Caenorhabditis elegans model"],"prefix":"10.1038","volume":"9","author":[{"given":"Tomoko","family":"Uehara","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidenori","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuhiko","family":"Okamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuro","family":"Kondoh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayesha","family":"Ahmad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bridget C.","family":"O\u2019Connor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sawako","family":"Yoshina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5710-2425","authenticated-orcid":false,"given":"Shohei","family":"Mitani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenjiro","family":"Kosaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7311-4135","authenticated-orcid":false,"given":"Toshiki","family":"Takenouchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,3,14]]},"reference":[{"key":"40988_CR1","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1002\/ajmg.a.37526","volume":"170A","author":"T Takenouchi","year":"2016","unstructured":"Takenouchi, T., Okamoto, N., Ida, S., Uehara, T. & Kosaki, K. 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