カトウ　タマキ   Katou Tamaki   加藤　環    所属   医学部 医学科（東京女子医科大学病院）    職種   講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	A synonymous splice site mutation in IL2RG gene causes late-onset combined immunodeficiency.
掲載誌名	正式名：International journal of hematology 略　 称：Int J Hematol ISSNコード：18653774/09255710
掲載区分	国外
巻・号・頁	109(5),pp.603-611
著者・共著者	Kato Tamaki
発行年月	2019/05
概要	X-Linked severe combined immunodeficiency (X-SCID) is a severe form of primary immunodeficiency characterized by absence of T cells and NK cells. X-SCID is caused by a loss-of-function mutation in the IL2RG gene that encodes common gamma chain (γc), which plays an essential role in lymphocyte development. We report the first case of hypomorphic X-SCID caused by a synonymous mutation in the IL2RG gene leading to a splice anomaly, in a family including two patients with diffuse cutaneous warts, recurrent molluscum contagiosum, and mild respiratory infections. The mutation caused aberrant splicing of IL2RG mRNA, subsequently resulted in reduced γc expression. The leaky production of normally spliced IL2RG mRNA produced undamaged protein; thus, T cells and NK cells were generated in the patients. Functional assays of the patients' T cells and NK cells revealed diminished cytokine response in the T cells and absent cytokine response in the NK cells. In addition, the TCR repertoire in these patients was limited. These data suggest that a fine balance between aberrant splicing and leaky production of normally spliced IL2RG mRNA resulted in late-onset combined immunodeficiency in these patients.
DOI	10.1007/s12185-019-02619-9
PMID	30850927