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. 2024 May 16;11(1):21.
doi: 10.1038/s41439-024-00277-w.

Characteristic craniofacial defects associated with a novel USP9X truncation mutation

Namiki Nagata  1 , Hiroshi Kurosaka  2 , Kotaro Higashi  3   4 , Masaya Yamaguchi  3   5   6   7 , Sayuri Yamamoto  1 , Toshihiro Inubushi  1 , Miho Nagata  8 , Yasuki Ishihara  8 , Ayumi Yonei  9 , Yohei Miyashita  8 , Yoshihiro Asano  8 , Norio Sakai  10 , Yasushi Sakata  8 , Shigetada Kawabata  3   7 , Takashi Yamashiro  1
Affiliations

Characteristic craniofacial defects associated with a novel USP9X truncation mutation

Namiki Nagata et al. Hum Genome Var. .

Abstract

Germline loss-of-function mutations in USP9X have been reported to cause a wide spectrum of congenital anomalies. Here, we report a Japanese girl with a novel heterozygous nonsense mutation in USP9X who exhibited intellectual disability with characteristic craniofacial abnormalities, including hypotelorism, brachycephaly, hypodontia, micrognathia, severe dental crowding, and an isolated submucous cleft palate. Our findings provide further evidence that disruptions in USP9X contribute to a broad range of congenital craniofacial abnormalities.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Clinical features of the present patient with a pathogenic mutation in USP9X.
Frontal (a) and lateral (b) views of the facial profile. Intraoral photos of the upper (c) and lower (d) jaws. e Underbite was observed in the occlusion. f Abnormal pigment pattern on the arm. g De novo nonsense mutation in the middle of the ubiquitin carboxyl-terminal hydrolase domain of USP9X. h The cryo-EM structure of USP9X (PDB ID: 7YXX). The ubiquitin carboxyl-terminal hydrolase domain is shown in cyan. The faded color indicates the truncated area in the mutated protein. i The crystal structure of the ubiquitin carboxyl-terminal hydrolase domain (PDB ID: 5WCH) is shown in magenta. His1879 and Asp1901 are missing in the mutated USP9X protein.
Fig. 2
Fig. 2. Craniofacial findings from radiographic records.
a Lateral cephalogram. b Orthopantomogram showing congenital missing teeth (yellow asterisk). CT of the head showed plagiocephaly (c) and an ectopically positioned left upper canine (d, red arrow).
See this image and copyright information in PMC

References

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