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Eur J Hum Genet. 2019 Mar;27(3):378-383. doi: 10.1038/s41431-018-0289-x. Epub 2018 Nov 28.

De novo truncating variants in PHF21A cause intellectual disability and craniofacial anomalies.

Author information

1
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, 236-0004, Japan.
2
Department of Pediatrics, Soka Municipal Hospital, Soka, Saitama, 340-8560, Japan.
3
Department of Neurosurgery, Okinawa Pref. Nanbu Medical Center and Children's Medical Center, Arakawa Haebaru, Okinawa, 901-1193, Japan.
4
Department of Medical Genetics, Haukeland University Hospital, Bergen, 5021, Norway.
5
Department of Pediatrics, Showa University School of Medicine, Tokyo, 142-8666, Japan.
6
Department of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, 431-3192, Japan.
7
Laboratory for Neurogenetics, RIKEN Center for Brain Science, Wako, Saitama, 351-0198, Japan.
8
Clinical Genetics Department, Yokohama City University Hospital, Yokohama, Kanagawa, 236-0004, Japan.
9
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, 236-0004, Japan. naomat@yokohama-cu.ac.jp.

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.

PMID:
30487643
PMCID:
PMC6460561
[Available on 2020-03-01]
DOI:
10.1038/s41431-018-0289-x
[Indexed for MEDLINE]

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