@article{6674889ea2374ccf99fc2cb96ad4a78a,
title = "Prevalence of germline GATA2 and SAMD9/9L variants in paediatric haematological disorders with monosomy 7",
abstract = "Monosomy 7 (−7) occurs in various types of paediatric myeloid disorders and has a poor prognosis. Recent studies have demonstrated that patients with germline gain-of-function SAMD9/9L variants and loss-of-function GATA2 variants are prone to developing myelodysplastic syndrome (MDS) associated with −7. However, the prevalence of the genetic variants among paediatric haematologic disorders with −7 is unknown. The present study screened germline variants of GATA2 and SAMD9/9L in 25 patients with various types of paediatric haematological disorders associated with −7. The diagnoses of the 25 patients included MDS (n = 10), acute myeloid leukaemia (AML) and myeloid sarcomas (n = 9), juvenile myelomonocytic leukaemia (n = 3) and other disorders (n = 3). Seven patients with a germline pathogenic GATA2 variant were found. For SAMD9/9L screening, next-generation sequencing was used to detect low-abundance variants and found four novel germline variants. Functional analysis revealed that three out of the four variants showed growth-restricting capacity in vitro and thus, were judged to be pathogenic. Cases with GATA2 mutation tended to be older, compared to those with SAMD9/9L mutations. In conclusion, GATA2 and SAMD9/9L were sequenced in 25 patients with paediatric haematologic disorders associated with −7, and 40% of them were found to have some pathogenic germline variants in the three genes.",
keywords = "GATA2, monosomy 7, pediatrics, SAMD9, SAMD9L",
author = "Masanori Yoshida and Kanako Tanase-Nakao and Hirohito Shima and Ryota Shirai and Kaoru Yoshida and Tomoo Osumi and Takao Deguchi and Makiko Mori and Yuki Arakawa and Masatoshi Takagi and Takako Miyamura and Kimiyoshi Sakaguchi and Hidemi Toyoda and Hisashi Ishida and Naoki Sakata and Toshihiko Imamura and Yuta Kawahara and Akira Morimoto and Takashi Koike and Hiroshi Yagasaki and Shuichi Ito and Daisuke Tomizawa and Nobutaka Kiyokawa and Satoshi Narumi and Motohiro Kato",
note = "Funding Information: The authors would like to thank Ms. Etsuko Mochizuki for her technical assistance. The authors thank the staff at the Center for Clinical Research and Development at NCCHD for their editorial support. This work was supported in part by the Japan Society for the Promotion of Science (JSPS) through a Grant‐in‐Aid for Scientific Research (grant number 17H04234 and 19H03627), the Japan Agency for Medical Research and development (AMED) (grant number 19ck0106467), Takeda Science Foundation, a Grant‐in‐Aid for Scientific Research on Innovative Areas from MEXT (3905‐A02), and a grant from the National Center for Child Health and Development (29‐2 and 2020A‐1). Publisher Copyright: {\textcopyright} 2020 British Society for Haematology and John Wiley & Sons Ltd",
year = "2020",
month = dec,
doi = "10.1111/bjh.17006",
language = "English",
volume = "191",
pages = "835--843",
journal = "British Journal of Haematology",
issn = "0007-1048",
publisher = "Wiley-Blackwell",
number = "5",
}