|
Yoshina Sawako
Department School of Medicine, School of Medicine Position Assistant Professor |
|
| Article types | Original article |
| Language | English |
| Peer review | Peer reviewed |
| Title | Pathogenetic basis of Takenouchi-Kosaki syndrome: Electron microscopy study using platelets in patients and functional studies in a Caenorhabditis elegans model. |
| Journal | Formal name：Scientific reports Abbreviation：Sci Rep ISSN code：(2045-2322)2045-2322(Linking) |
| Domestic / Foregin | Foregin |
| Volume, Issue, Page | 9(1),pp.4418 |
| Author and coauthor | Uehara Tomoko, Suzuki Hidenori, Okamoto Nobuhiko, Kondoh Tatsuro, Ahmad Ayesha, O'Connor Bridget C, Yoshina Sawako, Mitani Shohei, Kosaki Kenjiro, Takenouchi Toshiki |
| Publication date | 2019/03 |
| Summary | The combined phenotype of thrombocytopenia accompanied by intellectual disability in patients with a de novo heterozygous mutation, i.e., p.Tyr64Cys in CDC42, signifies a clinically recognizable novel syndrome that has been eponymized as "Takenouchi-Kosaki syndrome" (OMIM #616737). 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 α-granules were decreased, while vacuoles were increased. We further performed a functional analysis of p.Tyr64Cys in CDC42 through CRISPR/Cas9-mediated gene editing in a Caenorhabditis elegans 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 de novo mutation in CDC42, i.e., p.Tyr64Cys. |
| DOI | 10.1038/s41598-019-40988-7 |
| PMID | 30872706 |