Heterozygous Mutations in OAS1 Cause Infantile-Onset Pulmonary Alveolar Proteinosis with Hypogammaglobulinemia

Cho, Kazutoshi; Yamada, Masafumi; Agematsu, Kazunaga; Kanegane, Hirokazu; Miyake, Noriko; Ueki, Masahiro; Akimoto, Takuma; Kobayashi, Norimoto; Ikemoto, Satoru; Tanino, Mishie; Fujita, Atsushi; Hayasaka, Itaru; Miyamoto, Satoshi; Tanaka-Kubota, Mari; Nakata, Koh; Shiina, Masaaki; Ogata, Kazuhiro; Minakami, Hisanori; Matsumoto, Naomichi; Ariga, Tadashi

Heterozygous Mutations in OAS1 Cause Infantile-Onset Pulmonary Alveolar Proteinosis with Hypogammaglobulinemia

Cho, Kazutoshi; Yamada, Masafumi; Agematsu, Kazunaga et al.

The American Journal of Human Genetics, 2018, 102(3), 480-486

Permalink : https://hdl.handle.net/2115/71413

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アクセス権	open access
URI	https://hdl.handle.net/2115/71413
タイトル	Heterozygous Mutations in OAS1 Cause Infantile-Onset Pulmonary Alveolar Proteinosis with Hypogammaglobulinemia
著者	Cho, Kazutoshi ; Yamada, Masafumi ; Agematsu, Kazunaga ; Kanegane, Hirokazu ; Miyake, Noriko ; Ueki, Masahiro ; Akimoto, Takuma ; Kobayashi, Norimoto ; Ikemoto, Satoru ; Tanino, Mishie ; Fujita, Atsushi ; Hayasaka, Itaru ; Miyamoto, Satoshi ; Tanaka-Kubota, Mari ; Nakata, Koh ; Shiina, Masaaki ; Ogata, Kazuhiro ; Minakami, Hisanori ; Matsumoto, Naomichi ; Ariga, Tadashi
e-Rad_Researcher 10312365 著者名 Cho, Kazutoshi
著者名 Yamada, Masafumi
著者名 Agematsu, Kazunaga
著者名 Kanegane, Hirokazu
著者名 Miyake, Noriko
著者名 Ueki, Masahiro
著者名 Akimoto, Takuma
著者名 Kobayashi, Norimoto
著者名 Ikemoto, Satoru
e-Rad_Researcher 90360908 著者名 Tanino, Mishie
著者名 Fujita, Atsushi
著者名 Hayasaka, Itaru
著者名 Miyamoto, Satoshi
著者名 Tanaka-Kubota, Mari
著者名 Nakata, Koh
著者名 Shiina, Masaaki
著者名 Ogata, Kazuhiro
e-Rad_Researcher 40102256 著者名 Minakami, Hisanori
著者名 Matsumoto, Naomichi
e-Rad_Researcher 60322806 著者名 Ariga, Tadashi
言語	英語
キーワード	2',5'-oligoadenylate synthetase 1
	OAS1
	pulmonary alveolar proteinosis
	PAP
	hypogammaglobulinemia
	alveolar macrophage
発行日	2018-03-01
出版者	Cell Press
収録物名	The American Journal of Human Genetics
巻(号)	102(3)
ページ	480-486
抄録	Pulmonary alveolar proteinosis (PAP) is characterized by accumulation of a surfactant-like substance in alveolar spaces and hypoxemic respiratory failure. Genetic PAP (GPAP) is caused by mutations in genes encoding surfactant proteins or genes encoding a surfactant phospholipid transporter in alveolar type II epithelial cells. GPAP is also caused by mutations in genes whose products are implicated in surfactant catabolism in alveolar macrophages (AMs). We performed whole-exome sequence analysis in a family affected by infantile-onset PAP with hypogammaglobulinemia without causative mutations in genes associated with PAP: SFTPB, SFTPC, ABCA3, CSF2RA, CSF2RB, and GATA2. We identified a heterozygous missense variation in OAS1, encoding 2',5'-oligoadenylate synthetase 1 (OAS1) in three affected siblings, but not in unaffected family members. Deep sequence analysis with next-generation sequencing indicated 3.81% mosaicism of this variant in DNA from their mother's peripheral blood leukocytes, suggesting that PAP observed in this family could be inherited as an autosomal-dominant trait from the mother. We identified two additional de novo heterozygous missense variations of OAS1 in two unrelated simplex individuals also manifesting infantile-onset PAP with hypogammaglobulinemia. PAP in the two simplex individuals resolved after hematopoietic stem cell transplantation, indicating that OAS1 dysfunction is associated with impaired surfactant catabolism due to the defects in AMs.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
権利情報	© 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
PISSN	0002-9297
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1016/j.ajhg.2018.01.019