Abstract
Potocki–Shaffer syndrome (PSS) is a contiguous gene syndrome caused by 11p11.2 deletions. PSS is clinically characterized by intellectual disability, craniofacial anomalies, enlarged parietal foramina, and multiple exostoses. PSS occasionally shows autism spectrum disorder, epilepsy, and overgrowth. Some of the clinical features are thought to be associated with haploinsufficiency of two genes in the 11p11.2 region; variants affecting the function of ALX4 cause enlarged parietal foramina and EXT2 lead to multiple exostoses. However, the remaining clinical features were still yet to be linked to specific genetic alterations. In this study, we identified de novo truncating variants in an 11p11.2 gene, PHF21A, in three cases with intellectual disability and craniofacial anomalies. Among these three cases, autism spectrum disorder was recognized in one case, epilepsy in one case, and overgrowth in two cases. This study shows that PHF21A haploinsufficiency results in intellectual disability and craniofacial anomalies and possibly contributes to susceptibility to autism spectrum disorder, epilepsy, and overgrowth, all of which are PSS features.
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Acknowledgements
We thank all the participants for their cooperation in this research. We also thank Ms. K. Takabe, Mr. T. Miyama, Ms. N. Watanabe, Ms. M. Sato, Mr. S. Nakamura, and Ms. S. Sugimoto at the Department of Human Genetics, Yokohama City University Graduate School of Medicine, for their technical assistance. This work was supported by AMED under grant numbers, JP18ek0109280, JP18dm0107090, JP18ek0109301, JP18ek0109348, and JP18kk020500; JSPS KAKENHI Grant Numbers, JP17H01539, JP16H05160, JP16H05357, JP16H06254, JP15K10367, JP17K10080, JP 17K15630, and JP17H06994; the fund for Creation of Innovation Centers for Advanced Interdisciplinary Research Areas Program in the Project for Developing Innovation Systems (N Matsumoto) from the Japanese Science and Technology Agency; grants from the Ministry of Health, Labor and Welfare (N Matsumoto); the Takeda Science Foundation (N Miyake, HS, N. Matsumoto); and Kawano Masanori Memorial Public Interest Incorporated Foundation for Promotion of Pediatrics (S Miyatake). This study makes use of data generated by the DECIPHER community. A full list of centers who contributed to the generation of the data is available from http://decipher.sanger.ac.uk and via email from decipher@sanger.ac.uk.
Funding
Funding for the decipher project was provided by the Wellcome Trust. We thank Jeremy Allen, PhD, from Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript.
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Hamanaka, K., Sugawara, Y., Shimoji, T. et al. De novo truncating variants in PHF21A cause intellectual disability and craniofacial anomalies. Eur J Hum Genet 27, 378–383 (2019). https://doi.org/10.1038/s41431-018-0289-x
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DOI: https://doi.org/10.1038/s41431-018-0289-x
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