ヨシナ サワコ   Yoshina Sawako
  吉名 佐和子
   所属   医学部 医学科
   職種   講師
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 Pathogenetic basis of Takenouchi-Kosaki syndrome: Electron microscopy study using platelets in patients and functional studies in a Caenorhabditis elegans model.
掲載誌名 正式名:Scientific reports
略  称:Sci Rep
ISSNコード:(2045-2322)2045-2322(Linking)
掲載区分国外
巻・号・頁 9(1),4418頁
著者・共著者 Uehara Tomoko, Suzuki Hidenori, Okamoto Nobuhiko, Kondoh Tatsuro, Ahmad Ayesha, O'Connor Bridget C, Yoshina Sawako, Mitani Shohei, Kosaki Kenjiro, Takenouchi Toshiki
発行年月 2019/03
概要 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