Evidence map›Paper›PMID 41699395›Full record

ArticleScientific reports2026

Compound heterozygous CHAT gene mutations, a missense and a splice site variant, in two siblings with congenital myasthenic syndrome.

Shin Kikuchi, Nobuhiro Wada, Tasuku Mariya, Aki Ishikawa, Minako Kihara, Sawako Furukawa, Hidekazu Kato, Yosuke Nishio, Tomoo Ogi, Yuki Ohsaki and 1 more

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

Article in Scientific reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
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1 · What the graph read from it

What it found

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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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

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5 · Who and what money

Authors and funding

11 authors.

Shin KikuchiDivision of Cell and Tissue Morphology, Department of Anatomy, School of Medicine, Sapporo Medical University, South 1 West 17, Chuo-ku, Sapporo, Hokkaido, 060-8556, Japan. ksin@sapmed.ac.jp.
Nobuhiro WadaDivision of Cell and Tissue Morphology, Department of Anatomy, School of Medicine, Sapporo Medical University, South 1 West 17, Chuo-ku, Sapporo, Hokkaido, 060-8556, Japan.
Tasuku MariyaDepartment of Obstetrics and Gynecology, School of Medicine, Sapporo Medical University, Sapporo, 060-8556, Japan.
Aki IshikawaDivision of Clinical Genomics, Department of Genomic and Preventive Medicine, School of Medicine, Sapporo Medical University, Sapporo, 060-8556, Japan.
Minako KiharaDepartment of Pediatrics, Tomakomai City Hospital, Tomakomai, 053-8567, Japan.
Sawako FurukawaDepartment of Genetics, Research Institute of Environmental Medicine (RIeM), Nagoya University, Nagoya, 464-8601, Japan.
Hidekazu KatoDepartment of Genetics, Research Institute of Environmental Medicine (RIeM), Nagoya University, Nagoya, 464-8601, Japan.
Yosuke NishioDepartment of Genetics, Research Institute of Environmental Medicine (RIeM), Nagoya University, Nagoya, 464-8601, Japan.
Tomoo OgiDepartment of Genetics, Research Institute of Environmental Medicine (RIeM), Nagoya University, Nagoya, 464-8601, Japan.
Yuki OhsakiDivision of Cell and Tissue Morphology, Department of Anatomy, School of Medicine, Sapporo Medical University, South 1 West 17, Chuo-ku, Sapporo, Hokkaido, 060-8556, Japan.
Nobutada TachiDepartment of Health Sciences, Hokkaido Chitose College of Rehabilitation, Satomi 2-10, Chitose, 066-0055, Japan. tati@sapmed.ac.jp.

Funding

Japan Agency for Mecical Research and Development JP24ek0109760Japan Society for the Promotion of Science 22K11315Japan Society for the Promotion of Science 24K02208Japan Society for the Promotion of Science 25K21078
6 · The paper itself

Abstract

Mutations in the choline acetyltransferase (CHAT) gene cause congenital myasthenic syndrome (CMS). Episodic apnea is frequently observed in patients with CMS due to CHAT mutations (CMS-CHAT), and muscle hypotonia at birth or in early infancy is also common. We report two siblings with compound heterozygous mutations in the CHAT gene: c.1231G > A (missense) and c.752 + 2 T > C (splice site). To confirm the splice site mutation induces a splicing variant, we performed a minigene assay and demonstrated that the splice site mutation, c.752 + 2 T > C, results in complete exon skipping. AlphaFold2 analysis predicted that the skipped exon constitutes an α helix, a highly conserved core structural element of ChAT. These structural alterations in ChAT may underlie the clinical phenotype associated with these mutations.

Indexed as

Choline O-AcetyltransferaseMutation, MissenseMyasthenic Syndromes, CongenitalRNA Splice SitesExonsFemaleHeterozygoteHumansMaleSiblingsCholine O-AcetyltransferaseRNA Splice SitesCholine acetyltransferase (ChAT, CHAT)Congenital myasthenic syndrome (CMS)Minigene assaySplice-site mutation

Identifiers

PMID41699395
PMCPMC13002873

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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.