TY - JOUR
T1 - HECW2-related disorder in four Japanese patients
AU - Yanagishita, Tomoe
AU - Hirade, Takuya
AU - Shimojima Yamamoto, Keiko
AU - Funatsuka, Makoto
AU - Miyamoto, Yusaku
AU - Maeda, Makiko
AU - Yanagi, Kumiko
AU - Kaname, Tadashi
AU - Nagata, Satoru
AU - Nagata, Miho
AU - Ishihara, Yasuki
AU - Miyashita, Yohei
AU - Asano, Yoshihiro
AU - Sakata, Yasushi
AU - Kosaki, Kenjiro
AU - Yamamoto, Toshiyuki
N1 - Funding Information:
We appreciate the cooperation of the patients and their families for this study. This work was supported by Initiative on Rare and Undiagnosed Diseases (grant number 20ek0109301) from the Japan Agency for Medical Research and Development (AMED). We would also like to thank you for using “IRUD Exchange”, a database of variants via IRUD, for data sharing.
Publisher Copyright:
© 2021 Wiley Periodicals LLC.
PY - 2021/10
Y1 - 2021/10
N2 - The HECT, C2, and WW domain containing E3 ubiquitin protein ligase 2 gene (HECW2) is involved in protein ubiquitination. Several genes associated with protein ubiquitination have been linked to neurodevelopmental disorders. HECW2-related disorder has been established through the identification of de novo variants in HECW2 in patients with neurodevelopmental disorders with hypotonia, seizures, and absent language. Recently, we identified novel HECW2 variants in four Japanese patients with neurodevelopmental disorders. Regarding motor development, two of the patients cannot walk, whereas the other two can walk with an unsteady gait, owing to hypotonia. All HECW2 variants, including those that were previously reported, are missense, and no loss-of-function variants have been identified. Most of the identified variants are located around the HECT domain. These findings suggest that the dominant negative effects of missense variants around the HECT domain may be the mechanism underlying HECW2-related disorder.
AB - The HECT, C2, and WW domain containing E3 ubiquitin protein ligase 2 gene (HECW2) is involved in protein ubiquitination. Several genes associated with protein ubiquitination have been linked to neurodevelopmental disorders. HECW2-related disorder has been established through the identification of de novo variants in HECW2 in patients with neurodevelopmental disorders with hypotonia, seizures, and absent language. Recently, we identified novel HECW2 variants in four Japanese patients with neurodevelopmental disorders. Regarding motor development, two of the patients cannot walk, whereas the other two can walk with an unsteady gait, owing to hypotonia. All HECW2 variants, including those that were previously reported, are missense, and no loss-of-function variants have been identified. Most of the identified variants are located around the HECT domain. These findings suggest that the dominant negative effects of missense variants around the HECT domain may be the mechanism underlying HECW2-related disorder.
KW - abnormal behaviors
KW - de novo variant
KW - epilepsy
KW - exome sequencing
KW - intellectual disability
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U2 - 10.1002/ajmg.a.62363
DO - 10.1002/ajmg.a.62363
M3 - Article
C2 - 34047014
AN - SCOPUS:85106719362
SN - 1552-4825
VL - 185
SP - 2895
EP - 2902
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 10
ER -