Journal article
The recurrent postzygotic pathogenic variant p.Glu47Lys in RHOA causes a novel recognizable neuroectodermal phenotype
G Yigit, K Saida, D DeMarzo, N Miyake, A Fujita, T Yang Tan, SM White, A Wadley, MR Toliat, S Motameny, M Franitza, CA Stutterd, PF Chong, R Kira, T Sengoku, K Ogata, MJ Guillen Sacoto, C Fresen, BB Beck, P Nürnberg Show all
Human Mutation | WILEY-HINDAWI | Published : 2020
DOI: 10.1002/humu.23964
Abstract
RHOA is a member of the Rho family of GTPases that are involved in fundamental cellular processes including cell adhesion, migration, and proliferation. RHOA can stimulate the formation of stress fibers and focal adhesions and is a key regulator of actomyosin dynamics in various tissues. In a Genematcher-facilitated collaboration, we were able to identify four unrelated individuals with a specific phenotype characterized by hypopigmented areas of the skin, dental anomalies, body asymmetry, and limb length discrepancy due to hemihypotrophy of one half of the body, as well as brain magnetic resonance imaging (MRI) anomalies. Using whole-exome and ultra-deep amplicon sequencing and comparing ge..
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Awarded by Universität zu Köln
Funding Acknowledgements
We are grateful to all family members that participated in this study, Luise Graichen, Elisabeth Kirst, and Ramona Caspar for excellent technical assistance, and Karin Boss for critically reading the manuscript. Furthermore, we thank the Regional Computing Center of the University of Cologne (RRZK) for providing computing time on the Deutsche Forschungsgemeinschaft (DFG) funded high-performance computing system CHEOPS as well as support. This work was supported by AMED to N. Matsumoto; JSPS KAKENHI to N. Matsumoto and to N. Miyake; grants from the Ministry of Health, Labor, and Welfare to N. Matsumoto; grants from the Takeda Science Foundation to N. Matsumoto and N. Miyake; the DFG (German Research Foundation) under Germany's Excellence Strategy to B. Wollnik; the DFG (German Research Foundation)-Clinical research unit to J. Altmuller. This work was supported by the Japan Agency for Medical Research and Development (AMED), grant/award numbers: JP19ek0109280, JP19dm0107090, JP19ek0109301, JP19ek0109348, and JP18kk020501; Japan Society for the Promotion of Science (JSPS) KAKENHI, grant/award numbers: JP17H01539 and JP19H03621; Deutsche Forschungsgemeinschaft (DFG; German Research Foundation) under Germany's Excellence Strategy, grant/award number: EXC 2067/1-390729940; DFG (German Research Foundation), grant/award numbers: KFO 329, AL901/2-1, and AL901/3-1.