Cargando…
Pathogenetic basis of Takenouchi-Kosaki syndrome: Electron microscopy study using platelets in patients and functional studies in a Caenorhabditis elegans model
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 st...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418278/ https://www.ncbi.nlm.nih.gov/pubmed/30872706 http://dx.doi.org/10.1038/s41598-019-40988-7 |
_version_ | 1783403704238473216 |
---|---|
author | Uehara, Tomoko Suzuki, Hidenori Okamoto, Nobuhiko Kondoh, Tatsuro Ahmad, Ayesha O’Connor, Bridget C. Yoshina, Sawako Mitani, Shohei Kosaki, Kenjiro Takenouchi, Toshiki |
author_facet | Uehara, Tomoko Suzuki, Hidenori Okamoto, Nobuhiko Kondoh, Tatsuro Ahmad, Ayesha O’Connor, Bridget C. Yoshina, Sawako Mitani, Shohei Kosaki, Kenjiro Takenouchi, Toshiki |
author_sort | Uehara, Tomoko |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6418278 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-64182782019-03-18 Pathogenetic basis of Takenouchi-Kosaki syndrome: Electron microscopy study using platelets in patients and functional studies in a Caenorhabditis elegans model Uehara, Tomoko Suzuki, Hidenori Okamoto, Nobuhiko Kondoh, Tatsuro Ahmad, Ayesha O’Connor, Bridget C. Yoshina, Sawako Mitani, Shohei Kosaki, Kenjiro Takenouchi, Toshiki Sci Rep Article 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. Nature Publishing Group UK 2019-03-14 /pmc/articles/PMC6418278/ /pubmed/30872706 http://dx.doi.org/10.1038/s41598-019-40988-7 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Uehara, Tomoko Suzuki, Hidenori Okamoto, Nobuhiko Kondoh, Tatsuro Ahmad, Ayesha O’Connor, Bridget C. Yoshina, Sawako Mitani, Shohei Kosaki, Kenjiro Takenouchi, Toshiki Pathogenetic basis of Takenouchi-Kosaki syndrome: Electron microscopy study using platelets in patients and functional studies in a Caenorhabditis elegans model |
title | Pathogenetic basis of Takenouchi-Kosaki syndrome: Electron microscopy study using platelets in patients and functional studies in a Caenorhabditis elegans model |
title_full | Pathogenetic basis of Takenouchi-Kosaki syndrome: Electron microscopy study using platelets in patients and functional studies in a Caenorhabditis elegans model |
title_fullStr | Pathogenetic basis of Takenouchi-Kosaki syndrome: Electron microscopy study using platelets in patients and functional studies in a Caenorhabditis elegans model |
title_full_unstemmed | Pathogenetic basis of Takenouchi-Kosaki syndrome: Electron microscopy study using platelets in patients and functional studies in a Caenorhabditis elegans model |
title_short | Pathogenetic basis of Takenouchi-Kosaki syndrome: Electron microscopy study using platelets in patients and functional studies in a Caenorhabditis elegans model |
title_sort | pathogenetic basis of takenouchi-kosaki syndrome: electron microscopy study using platelets in patients and functional studies in a caenorhabditis elegans model |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418278/ https://www.ncbi.nlm.nih.gov/pubmed/30872706 http://dx.doi.org/10.1038/s41598-019-40988-7 |
work_keys_str_mv | AT ueharatomoko pathogeneticbasisoftakenouchikosakisyndromeelectronmicroscopystudyusingplateletsinpatientsandfunctionalstudiesinacaenorhabditiselegansmodel AT suzukihidenori pathogeneticbasisoftakenouchikosakisyndromeelectronmicroscopystudyusingplateletsinpatientsandfunctionalstudiesinacaenorhabditiselegansmodel AT okamotonobuhiko pathogeneticbasisoftakenouchikosakisyndromeelectronmicroscopystudyusingplateletsinpatientsandfunctionalstudiesinacaenorhabditiselegansmodel AT kondohtatsuro pathogeneticbasisoftakenouchikosakisyndromeelectronmicroscopystudyusingplateletsinpatientsandfunctionalstudiesinacaenorhabditiselegansmodel AT ahmadayesha pathogeneticbasisoftakenouchikosakisyndromeelectronmicroscopystudyusingplateletsinpatientsandfunctionalstudiesinacaenorhabditiselegansmodel AT oconnorbridgetc pathogeneticbasisoftakenouchikosakisyndromeelectronmicroscopystudyusingplateletsinpatientsandfunctionalstudiesinacaenorhabditiselegansmodel AT yoshinasawako pathogeneticbasisoftakenouchikosakisyndromeelectronmicroscopystudyusingplateletsinpatientsandfunctionalstudiesinacaenorhabditiselegansmodel AT mitanishohei pathogeneticbasisoftakenouchikosakisyndromeelectronmicroscopystudyusingplateletsinpatientsandfunctionalstudiesinacaenorhabditiselegansmodel AT kosakikenjiro pathogeneticbasisoftakenouchikosakisyndromeelectronmicroscopystudyusingplateletsinpatientsandfunctionalstudiesinacaenorhabditiselegansmodel AT takenouchitoshiki pathogeneticbasisoftakenouchikosakisyndromeelectronmicroscopystudyusingplateletsinpatientsandfunctionalstudiesinacaenorhabditiselegansmodel |