title: Macrothrombocytopenia and developmental delay with a de novo CDC42 mutation: Yet another locus for thrombocytopenia and developmental delay.
abstract: The combinatory phenotype of thrombocytopenia and developmental delay has been described for two genetic conditions: a chromosome 11q deletion that is referred to as Jacobsen syndrome, and a 21q22 microdeletion syndrome. Herein, we report a young girl who presented with persistent macrothrombocytopenia and a developmental delay. Whole exome sequencing revealed a de novo amino acid substitution in CDC42, a critical regulator of the cytoskeleton. Our observation recapitulates observations in mice lacking Cdc42. We suggest that this CDC42 mutation may represent yet another mechanism leading to the combinatory phenotype of persistent macrothrombocytopenia and developmental delay.
authors.affiliation: Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan.|Center for Medical Genetics, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Takenouchi
authors.affiliation: Division of Medical Genetics, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Rika
authors.initials: R
authors.lastname: Kosaki
authors.affiliation: Department of Pediatrics, Tokyo Rinkai Hospital, Tokyo, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Niizuma
authors.affiliation: Department of Maternal-Fetal Biology, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Hata
authors.affiliation: Center for Medical Genetics, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kosaki
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002658:Developmental Disabilities / Q000097:blood / Q000150:complications / Q000235:genetics*; D019066:Facies; D005260:Female; D056426:Genetic Loci; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D009154:Mutation / Q000235:genetics*; D013921:Thrombocytopenia / Q000097:blood / Q000150:complications / Q000235:genetics*; D020764:cdc42 GTP-Binding Protein / Q000235:genetics*
chemical_list: D020764:cdc42 GTP-Binding Protein
keywords: CDC42; Wiskott-Aldrich syndrome; cytoskeleton; developmental delay; exome sequencing; thrombocytopenia