Evidence map›Paper›PMID 42599553›Full record

ArticleNeurogenetics2026

Novel deep intronic variant in CLCN1 causing autosomal recessive myotonia congenita.

Shaimaa Helal, Neta Pipko, Yijing Liang, Adrian Levine, Amanda Carnevale, Anna Szuto, Christian R Marshall, Gregory Costain, Ashish R Deshwar, Grace Yoon

Abstract readCase Reports
PubMed Publisher
In one paragraph

Article in Neurogenetics, 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
–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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

10 authors.

Shaimaa HelalDivision of Clinical and Metabolic Genetics, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
Neta PipkoProgram in Genetics and Genome Biology, SickKids Research Institute, Toronto, ON, Canada.
Yijing LiangProgram in Genetics and Genome Biology, SickKids Research Institute, Toronto, ON, Canada.
Adrian LevineDivision of Pathology, Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Canada.
Amanda CarnevaleDivision of Clinical and Metabolic Genetics, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
Anna SzutoDivision of Clinical and Metabolic Genetics, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
Christian R MarshallProgram in Genetics and Genome Biology, SickKids Research Institute, Toronto, ON, Canada.
Gregory CostainDivision of Clinical and Metabolic Genetics, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
Ashish R DeshwarDivision of Clinical and Metabolic Genetics, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
Grace YoonDivision of Clinical and Metabolic Genetics, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada. grace.yoon@utoronto.ca.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Myotonia congenita is a skeletal muscle channelopathy caused by pathogenic variants in CLCN1, encoding the ClC-1 chloride channel. We report two sisters with clinical features consistent with recessive myotonia congenita and compound heterozygous variants in CLCN1 identified through short-read genome sequencing: a paternally inherited pathogenic missense variant c.871G > A (p.Glu291Lys) and a novel maternally inherited deep intronic variant, c.697-620 T > G. RNA sequencing of a muscle biopsy revealed that the deep intronic variant activates a cryptic splice donor site, resulting in inclusion of an out-of-frame cryptic exon, multiple aberrant splice junctions and partial nonsense mediated decay. Allele-specific expression analysis showed a 70:30 skew favouring the paternal allele, supporting degradation of the maternally-derived transcript. These findings confirm the likely pathogenicity of c.697-620 T > G as a novel loss-of-function variant in CLCN1 and expand the spectrum of CLCN1-related autosomal recessive myotonia congenita.

Indexed as

Chloride ChannelsIntronsMyotonia CongenitaChildFemaleGenes, RecessiveHumansMutation, MissensePedigreeChloride ChannelsCLC-1 channelChloride channelMyotonia congenitaRNA sequencingSplicing

Identifiers

PMID42599553

What OpenQuestion holds

Textmetadata
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.