Variant spectrum of PIEZO1 and KCNN4 in Japanese patients with dehydrated hereditary stomatocytosis

Erina Nakahara; Keiko Shimojima Yamamoto; Hiromi Ogura; Takako Aoki; Taiju Utsugisawa; Kenko Azuma; Hiroyuki Akagawa; Kenichiro Watanabe; Michiko Muraoka; Fumihiko Nakamura; Michi Kamei; Koji Tatebayashi; Jun Shinozuka; Takahisa Yamane; Makoto Hibino; Yoshiya Katsura; Sonoko Nakano-Akamatsu; Norimitsu Kadowaki; Yoshiro Maru; Etsuro Ito; Shouichi Ohga; Hiroshi Yagasaki; Ichiro Morioka; Toshiyuki Yamamoto; Hitoshi Kanno

doi:10.1038/s41439-023-00235-y

Variant spectrum of PIEZO1 and KCNN4 in Japanese patients with dehydrated hereditary stomatocytosis

Hum Genome Var. 2023 Mar 2;10(1):8. doi: 10.1038/s41439-023-00235-y.

Authors

Erina Nakahara^{1

2}, Keiko Shimojima Yamamoto^{3

4

5}, Hiromi Ogura¹, Takako Aoki¹, Taiju Utsugisawa¹, Kenko Azuma⁶, Hiroyuki Akagawa⁶, Kenichiro Watanabe⁷, Michiko Muraoka⁸, Fumihiko Nakamura⁹, Michi Kamei¹⁰, Koji Tatebayashi¹¹, Jun Shinozuka¹², Takahisa Yamane¹³, Makoto Hibino¹⁴, Yoshiya Katsura¹⁵, Sonoko Nakano-Akamatsu¹⁶, Norimitsu Kadowaki¹⁷, Yoshiro Maru¹⁸, Etsuro Ito¹⁹, Shouichi Ohga²⁰, Hiroshi Yagasaki², Ichiro Morioka², Toshiyuki Yamamoto^{6

21}, Hitoshi Kanno¹

Affiliations

¹ Department of Transfusion Medicine and Cell Processing, Tokyo Women's Medical University, Tokyo, Japan.
² Department of Pediatrics and Child Health, Nihon University School of Medicine, Tokyo, Japan.
³ Department of Transfusion Medicine and Cell Processing, Tokyo Women's Medical University, Tokyo, Japan. shimojima.keiko@twmu.ac.jp.
⁴ Institute for Comprehensive Medical Sciences, Tokyo Women's Medical University, Tokyo, Japan. shimojima.keiko@twmu.ac.jp.
⁵ Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, Japan. shimojima.keiko@twmu.ac.jp.
⁶ Institute for Comprehensive Medical Sciences, Tokyo Women's Medical University, Tokyo, Japan.
⁷ Department of Hematology and Oncology, Shizuoka Children's Hospital, Shizuoka, Japan.
⁸ Department of Pediatrics, Fukuyama Medical Center, Okayama, Japan.
⁹ Department of Laboratory Medicine, Nara Prefecture General Medical Center, Nara, Japan.
¹⁰ Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
¹¹ Department of Neonatology, Gifu Prefectural General Medical Center, Gifu, Japan.
¹² Department of Pediatrics, Uji-Tokushukai Medical Center, Kyoto, Japan.
¹³ Department of Hematology, Osaka City General Hospital, Osaka, Japan.
¹⁴ Department of Respiratory Medicine, Shonan Fujisawa Tokushukai Hospital, Fujisawa, Kanagawa, Japan.
¹⁵ Department of Metabolism and Endocrinology, Tokyo Medical University Ibaraki Medical Center, Ibaraki, Japan.
¹⁶ Department of Hematology, Omihachiman Community Medical Center, Shiga, Japan.
¹⁷ Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan.
¹⁸ Department of Pharmacology, Tokyo Women's Medical University, Tokyo, Japan.
¹⁹ Department of Pediatrics, Hirosaki University Graduate School of Medicine, Aomori, Japan.
²⁰ Department of Pediatrics, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
²¹ Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, Japan.

Abstract

Hereditary stomatocytosis (HSt) is a type of congenital hemolytic anemia caused by abnormally increased cation permeability of erythrocyte membranes. Dehydrated HSt (DHSt) is the most common subtype of HSt and is diagnosed based on clinical and laboratory findings related to erythrocytes. PIEZO1 and KCNN4 have been recognized as causative genes, and many related variants have been reported. We analyzed the genomic background of 23 patients from 20 Japanese families suspected of having DHSt using a target capture sequence and identified pathogenic/likely pathogenic variants of PIEZO1 or KCNN4 in 12 families.