Hydrops fetalis due to loss of function of hNav1.4 channel via compound heterozygous variants

Kubota, Tomoya; Nagata, Miho; Takagi, Kazuko; Ishihara, Yasuki; Kojima, Kurumi; Uchikura, Yuka; Yamamoto, Reina; Yonei, Ayumi; Ozaki, Erina; Kira, Natsuki; Takahashi, Satoe; Homma, Kazuaki; Miyashita, Yohei; Eguchi-Ishimae, Minenori; Sakai, Norio; Asano, Yoshihiro; Sakata, Yasushi; Ozono, Keiichi; Eguchi, Mariko; Takahashi, Masanori P.

doi:https://doi.org/10.1038/s10038-024-01284-z

Hydrops fetalis due to loss of function of hNav1.4 channel via compound heterozygous variants

Kubota, Tomoya; Nagata, Miho; Takagi, Kazuko et al.

Journal of Human Genetics, 2024, 70(1), 3-8

アクセス数:1,870件（2025-07-02 19:57 集計）

固定URL: https://hdl.handle.net/11094/98112

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タイトル	Hydrops fetalis due to loss of function of hNav1.4 channel via compound heterozygous variants
著者	NRID 1000020573231 1000020573231 ORCID 0000-0003-1004-8537 0000-0003-1004-8537 researchmap permalink n-phys n-phys Scopus Author ID 26633163700 26633163700 著者名 Kubota, Tomoya
	著者名 Nagata, Miho
	NRID 1000080648626 1000080648626 著者名 Takagi, Kazuko
	NRID 1000000886525 1000000886525 ORCID 0000-0002-0307-238X 0000-0002-0307-238X researchmap permalink yskishr yskishr 著者名 Ishihara, Yasuki
	著者名 Kojima, Kurumi
	NRID 1000050648623 1000050648623 著者名 Uchikura, Yuka
	著者名 Yamamoto, Reina
	著者名 Yonei, Ayumi
	著者名 Ozaki, Erina
	著者名 Kira, Natsuki
	著者名 Takahashi, Satoe
	著者名 Homma, Kazuaki
	NRID 1000060816312 1000060816312 ORCID 0000-0002-1739-4734 0000-0002-1739-4734 researchmap permalink y-miyashita y-miyashita Scopus Author ID 57208672131 57208672131 著者名 Miyashita, Yohei
	NRID 1000050420782 1000050420782 著者名 Eguchi-Ishimae, Minenori
	NRID 1000030314313 1000030314313 researchmap permalink norio_sakai1121 norio_sakai1121 著者名 Sakai, Norio
	NRID 1000060527670 1000060527670 researchmap permalink osaka-med-yasano osaka-med-yasano Scopus Author ID 7401729290 7401729290 著者名 Asano, Yoshihiro
	NRID 1000000397671 1000000397671 ORCID 0000-0002-5618-4721 0000-0002-5618-4721 researchmap permalink C4589 C4589 Scopus Author ID 35395964700 35395964700 著者名 Sakata, Yasushi
	NRID 1000020270770 1000020270770 researchmap permalink read0092357 read0092357 Scopus Author ID 55545335700 55545335700 著者名 Ozono, Keiichi
	NRID 1000040420781 1000040420781 著者名 Eguchi, Mariko
	NRID 1000020359847 1000020359847 researchmap permalink mtakahas mtakahas Scopus Author ID 15038719500 15038719500 著者名 Takahashi, Masanori P.
内容	Kubota T., Nagata M., Takagi K., et al. Hydrops fetalis due to loss of function of hNav1.4 channel via compound heterozygous variants. Journal of Human Genetics, (2024); https://doi.org/10.1038/s10038-024-01284-z.
抄録	Hydrops fetalis, characterized by abnormal fluid accumulation in fetuses, presents a significant risk of stillbirth and neonatal mortality. Although the etiology of nonimmune hydrops fetalis (NIHF) is multifaceted, recent studies have highlighted genetic factors as crucial determinants. This study focused on a family with three consecutive stillbirths, each with pronounced hydrops fetalis. Using whole-exome sequencing (WES), we identified compound heterozygous variants of the SCN4A gene encoding the voltage-gated sodium channel of the skeletal muscle (hNav1.4), c.2429T>A p.L810Q and c.4556T>C p.F1519S, in all three deceased infants. A functional analysis conducted using the whole-cell patch-clamp technique revealed loss-of-function defects in both variant channels, with F1519S exhibiting a complete loss of ionic current and L810Q showing a reduced channel opening. These findings support the pathogenicity of SCN4A variants in NIHF and underscore the significance of functional studies in elucidating genotype-phenotype correlations. Furthermore, our study emphasizes the diagnostic value of WES in cases of NIHF in where standard genetic testing fails to identify causative variants.
出版者	Springer Nature
収録物名	Journal of Human Genetics
巻(号)	70(1)
ページ	3-8
刊行年月	2024-08-21
言語	英語
ハンドルURL	https://hdl.handle.net/11094/98112
PISSN	14345161
eISSN	1435232X
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1038/s10038-024-01284-z
アクセス権	open access
権利情報	This article is licensed under a Creative Commons Attribution 4.0 International License.
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCTERMS.bibliographicCitation	Journal of Human Genetics. 2024, 70(1), p. 3-8
DC.title	Hydrops fetalis due to loss of function of hNav1.4 channel via compound heterozygous variants
DC.creator	Kubota, Tomoya
	Nagata, Miho
	Takagi, Kazuko
	Ishihara, Yasuki
	Kojima, Kurumi
	Uchikura, Yuka
	Yamamoto, Reina
	Yonei, Ayumi
	Ozaki, Erina
	Kira, Natsuki
	Takahashi, Satoe
	Homma, Kazuaki
	Miyashita, Yohei
	Eguchi-Ishimae, Minenori
	Sakai, Norio
	Asano, Yoshihiro
	Sakata, Yasushi
	Ozono, Keiichi
	Eguchi, Mariko
	Takahashi, Masanori P.
DC.publisher	Springer Nature
DC.language' scheme='DCTERMS.RFC1766	英語
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2024-08-21
DC.identifier	https://doi.org/10.1038/s10038-024-01284-z
DC.description	Kubota T., Nagata M., Takagi K., et al. Hydrops fetalis due to loss of function of hNav1.4 channel via compound heterozygous variants. Journal of Human Genetics, (2024); https://doi.org/10.1038/s10038-024-01284-z.
DCTERMS.abstract	Hydrops fetalis, characterized by abnormal fluid accumulation in fetuses, presents a significant risk of stillbirth and neonatal mortality. Although the etiology of nonimmune hydrops fetalis (NIHF) is multifaceted, recent studies have highlighted genetic factors as crucial determinants. This study focused on a family with three consecutive stillbirths, each with pronounced hydrops fetalis. Using whole-exome sequencing (WES), we identified compound heterozygous variants of the SCN4A gene encoding the voltage-gated sodium channel of the skeletal muscle (hNav1.4), c.2429T>A p.L810Q and c.4556T>C p.F1519S, in all three deceased infants. A functional analysis conducted using the whole-cell patch-clamp technique revealed loss-of-function defects in both variant channels, with F1519S exhibiting a complete loss of ionic current and L810Q showing a reduced channel opening. These findings support the pathogenicity of SCN4A variants in NIHF and underscore the significance of functional studies in elucidating genotype-phenotype correlations. Furthermore, our study emphasizes the diagnostic value of WES in cases of NIHF in where standard genetic testing fails to identify causative variants.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	98112
citation_title	Hydrops fetalis due to loss of function of hNav1.4 channel via compound heterozygous variants
citation_author	Kubota, Tomoya
	Nagata, Miho
	Takagi, Kazuko
	Ishihara, Yasuki
	Kojima, Kurumi
	Uchikura, Yuka
	Yamamoto, Reina
	Yonei, Ayumi
	Ozaki, Erina
	Kira, Natsuki
	Takahashi, Satoe
	Homma, Kazuaki
	Miyashita, Yohei
	Eguchi-Ishimae, Minenori
	Sakai, Norio
	Asano, Yoshihiro
	Sakata, Yasushi
	Ozono, Keiichi
	Eguchi, Mariko
	Takahashi, Masanori P.
citation_publisher	Springer Nature
citation_language	英語
citation_date	2024-08-21
citation_journal_title	Journal of Human Genetics
citation_volume	70
citation_issue	1
citation_firstpage	3
citation_lastpage	8
citation_doi	https://doi.org/10.1038/s10038-024-01284-z
citation_public_url	https://hdl.handle.net/11094/98112

Hydrops fetalis due to loss of function of hNav1.4 channel via compound heterozygous variants

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