Evidence map›Paper›PMID 39164360›Full record

ArticleJournal of human genetics2025

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

Tomoya Kubota, Miho Nagata, Kazuko Takagi, Yasuki Ishihara, Kurumi Kojima, Yuka Uchikura, Reina Yamamoto, Ayumi Yonei, Erina Ozaki, Natsuki Kira and 10 more

Abstract readCase Reports
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of human genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors.

Tomoya Kubota *Clinical Neurophysiology, Department of Clinical Laboratory and Biomedical Sciences, Osaka University Graduate School of Medicine, Suita, Osaka, 5650871, Japan.
Miho Nagata *Department of Cardiovascular Medicine (IRUD Analysis Center), Osaka University Graduate School of Medicine, Suita, Osaka, 5650871, Japan.
Kazuko TakagiDepartment of Obstetrics and Gynecology, Ehime University Graduate School of Medicine, Touon, Ehime, 7910295, Japan.
Yasuki IshiharaDepartment of Cardiovascular Medicine (IRUD Analysis Center), Osaka University Graduate School of Medicine, Suita, Osaka, 5650871, Japan.
Kurumi KojimaClinical Neurophysiology, Department of Clinical Laboratory and Biomedical Sciences, Osaka University Graduate School of Medicine, Suita, Osaka, 5650871, Japan.
Yuka UchikuraDepartment of Obstetrics and Gynecology, Ehime University Graduate School of Medicine, Touon, Ehime, 7910295, Japan.
Reina YamamotoClinical Neurophysiology, Department of Clinical Laboratory and Biomedical Sciences, Osaka University Graduate School of Medicine, Suita, Osaka, 5650871, Japan.
Ayumi YoneiDivision of Genetic Counselling, Osaka University Hospital, Suita, Osaka, 5650871, Japan.
Erina OzakiDivision of Medical Genetics, Ehime University Hospital, Touon, Ehime, 7910295, Japan.
Natsuki KiraClinical Neurophysiology, Department of Clinical Laboratory and Biomedical Sciences, Osaka University Graduate School of Medicine, Suita, Osaka, 5650871, Japan.
Satoe TakahashiDepartment of Otolaryngology-Head and Neck Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.
Kazuaki HommaDepartment of Otolaryngology-Head and Neck Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.ORCID http://orcid.org/0000-0002-4440-2277
Yohei MiyashitaDepartment of Cardiovascular Medicine (IRUD Analysis Center), Osaka University Graduate School of Medicine, Suita, Osaka, 5650871, Japan.
Minenori Eguchi-IshimaeDivision of Medical Genetics, Ehime University Hospital, Touon, Ehime, 7910295, Japan.
Norio SakaiDivision of Genetic Counselling, Osaka University Hospital, Suita, Osaka, 5650871, Japan.
Yohihiro AsanoDepartment of Cardiovascular Medicine (IRUD Analysis Center), Osaka University Graduate School of Medicine, Suita, Osaka, 5650871, Japan. asano.yoshihiro@ncvc.go.jp.
Yasushi SakataDepartment of Cardiovascular Medicine (IRUD Analysis Center), Osaka University Graduate School of Medicine, Suita, Osaka, 5650871, Japan.
Keiichi OzonoDepartment of Pediatrics, Osaka University Graduate School of Medicine, Suita, Osaka, 5650871, Japan.ORCID http://orcid.org/0000-0002-6517-8825
Mariko EguchiDivision of Medical Genetics, Ehime University Hospital, Touon, Ehime, 7910295, Japan. eguchi.mariko.my@ehime-u.ac.jp.ORCID http://orcid.org/0000-0001-8727-1732
Masanori P TakahashiClinical Neurophysiology, Department of Clinical Laboratory and Biomedical Sciences, Osaka University Graduate School of Medicine, Suita, Osaka, 5650871, Japan. mtakahas@sahs.med.osaka-u.ac.jp.ORCID http://orcid.org/0000-0002-5513-5012

Funding

Defining the pathological mechanisms of hereditary hearing lossR01DC017482 · NIDCD · NORTHWESTERN UNIVERSITY AT CHICAGO · PI HOMMA, KAZUAKI · 2019 to 2023
$1.7M
Japan Agency for Medical Research and Development (AMED) JP21ek0109549Ministry of Health, Labour and Welfare (Ministry of Health, Labour and Welfare, Japan) JP21FC1006Ministry of Health, Labour and Welfare (Ministry of Health, Labour and Welfare, Japan) JP23FC1014NIDCD NIH HHS R01 DC017482U.S. Department of Health & Human Services | National Institutes of Health (NIH) DC017482
6 · The paper itself

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.

Indexed as

HeterozygoteHydrops FetalisNAV1.4 Voltage-Gated Sodium ChannelExome SequencingFemaleGenetic Association StudiesHumansLoss of Function MutationPedigreePregnancyStillbirthNAV1.4 Voltage-Gated Sodium ChannelSCN4A protein, human

Identifiers

PMID39164360
PMCPMC11700836

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.