Evidence map›Paper›PMID 39948543›Full record

Observational studyFluids and barriers of the CNS2025

Low prevalence of CWH43 variants among Finnish and Norwegian idiopathic normal pressure hydrocephalus patients: a cohort-based observational study.

Joel Räsänen, Seppo Helisalmi, Sami Heikkinen, Joose Raivo, Ville E Korhonen, Henna Martiskainen, Antti Junkkari, Benjamin Grenier-Boley, Céline Bellenguez, Minna Oinas and 24 more

Abstract readObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Fluids and barriers of the CNS, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed, 1 pooled it
–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

2 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. 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

34 authors.

Joel Räsänen *Department of Neurosurgery, Kuopio University Hospital and Institute of Clinical Medicine - Neurosurgery, University of Eastern Finland, P.O.Box 100, 70029, Kuopio, KYS, Finland.
Seppo Helisalmi *Faculty of Health Sciences, School of Medicine, Institute of Clinical Medicine, University of Eastern Finland, Genome Center of Eastern Finland, Kuopio, Finland.
Sami HeikkinenInstitute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
Joose RaivoFaculty of Health Sciences, School of Medicine, Institute of Clinical Medicine, University of Eastern Finland, Genome Center of Eastern Finland, Kuopio, Finland.
Ville E KorhonenDepartment of Neurosurgery, Kuopio University Hospital and Institute of Clinical Medicine - Neurosurgery, University of Eastern Finland, P.O.Box 100, 70029, Kuopio, KYS, Finland.
Henna MartiskainenInstitute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
Antti JunkkariDepartment of Neurology, Clinical Neurosciences, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
Benjamin Grenier-BoleyU1167-RID-AGE Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement, Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, France.
Céline BellenguezU1167-RID-AGE Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement, Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, France.
Minna OinasDepartment of Neurosurgery, Kuopio University Hospital and Institute of Clinical Medicine - Neurosurgery, University of Eastern Finland, P.O.Box 100, 70029, Kuopio, KYS, Finland.
Cecilia AvellanNeurocenter, Department of Neurosurgery, University Hospital of Turku and Clinical Neurosciences, University of Turku, Turku, Finland.
Janek FrantzenNeurocenter, Department of Neurosurgery, University Hospital of Turku and Clinical Neurosciences, University of Turku, Turku, Finland.
Anna KotkansaloNeurocenter, Department of Neurosurgery, University Hospital of Turku and Clinical Neurosciences, University of Turku, Turku, Finland.
Jaakko RinneNeurocenter, Department of Neurosurgery, University Hospital of Turku and Clinical Neurosciences, University of Turku, Turku, Finland.
Antti RonkainenDepartment of Neurosurgery, Tampere University Hospital, Tampere, Finland.
Mikko KauppinenUnit of Clinical Neuroscience, Neurosurgery, University of Oulu and Medical Research Center, Oulu University Hospital, Oulu, Finland.
Mikael von Und Zu FraunbergUnit of Clinical Neuroscience, Neurosurgery, University of Oulu and Medical Research Center, Oulu University Hospital, Oulu, Finland.
Kimmo LönnrotDepartment of Neurosurgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Jarno SatopääDepartment of Neurosurgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Markus PerolaFinnish Institute for Health and Welfare (THL), Helsinki, Finland.
Anne M KoivistoDepartment of Neurosciences, University of Helsinki, Helsinki, Finland.
Valtteri JulkunenInstitute of Clinical Medicine - Neurology, University of Eastern Finland, Kuopio, Finland.
Anne M PortaankorvaDepartment of Neurosciences, University of Helsinki, Helsinki, Finland.
Arto MannermaaSchool of Medicine, Institute of Clinical Medicine, Pathology and Forensic Medicine, and Translational Cancer Research Area, University of Eastern Finland, Kuopio, Finland.
Hilkka SoininenInstitute of Clinical Medicine - Neurology, University of Eastern Finland, Kuopio, Finland.
Juha E JääskeläinenDepartment of Neurosurgery, Kuopio University Hospital and Institute of Clinical Medicine - Neurosurgery, University of Eastern Finland, P.O.Box 100, 70029, Kuopio, KYS, Finland.
Jean-Charles LambertU1167-RID-AGE Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement, Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, France.
Per K EideDepartment of Neurosurgery, Oslo University Hospital-Rikshospitalet, Oslo, Norway.
FinnGen
Aarno PalotieInstitute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland.
Mitja I KurkiAnalytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, USA.
Mikko HiltunenInstitute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
Ville LeinonenDepartment of Neurosurgery, Kuopio University Hospital and Institute of Clinical Medicine - Neurosurgery, University of Eastern Finland, P.O.Box 100, 70029, Kuopio, KYS, Finland. ville.leinonen@kuh.fi.
Anssi LipponenInstitute of Biomedicine, University of Eastern Finland, Kuopio, Finland.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHeterozygous CWH43 loss-of-function (LOF) variants have been identified as iNPH risk factors, with 10-15% of iNPH patients carrying these variants in cohorts from the US. Mouse model harboring CWH43 LOF variants display a hydrocephalic phenotype with ventricular cilia alterations. Our aim was to study the effect of CWH43 variants on disease risk and clinical phenotype in Finnish and Norwegian iNPH cohorts.

methodsWe analyzed CWH43 LOF frameshift deletions (4:49032652 CA/C, Leu533Ter and 4:49061875 CA/C, Lys696AsnfsTer23) in Finnish iNPH patients from the Kuopio NPH registry (n = 630) and FinnGen (iNPH n = 1 131, controls n = 495 400), and Norwegian iNPH patients from EADB (n = 306). The Kuopio and Norwegian cohorts included possible and probable iNPH patients based on the American-European iNPH guidelines. FinnGen cohort included iNPH patients based on ICD-10 G91.2 with the exclusion of secondary etiologies, and controls having no diagnosis of hydrocephalus.

resultsIn the Kuopio cohort of Finnish iNPH patients, 2.9% carried CWH43 variants (Leu533Ter 2.1%, Lys696AsnfsTer23 0.8%), with one homozygous Leu533Ter carrier. In FinnGen, 3.1% of iNPH patients carried heterozygous variants (Leu533Ter 2.6%, Lys696AsnfsTer23 0.5%) compared to 2.5% of controls (p = 0.219, OR = 1.23, 95% CI 0.85-1.72), with no effect on disease risk or onset age. Importantly in the FinnGen cohort, none of the 23 compound heterozygote or 59 homozygote individuals had hydrocephalus diagnosis. In the Norwegian iNPH cohort, 5.2% of patients were heterozygous variant carriers (Leu533Ter 3.3%, Lys696AsnfsTer23 2.0%). No differences in clinical phenotype (age, triad symptoms, shunt response, vascular comorbidities) were found between carriers and noncarriers in any cohort. However, 74% of variant-carrying iNPH patients in FinnGen were female, compared to 47% of noncarriers (p = 0.002). Pedigrees indicated no autosomal dominant co-inheritance of iNPH and the CWH43 variants.

conclusionsWe studied the iNPH-associated CWH43 LOF variants for the first time on a population-scale. Contrary to previously reported findings in smaller cohorts, our study revealed a low prevalence of these variants in the population-scale Finnish iNPH cohort, with no effect on disease risk of iNPH. The prevalence in the Norwegian iNPH cohort was also low compared to previous studies.

Indexed as

Hydrocephalus, Normal PressureAdultAgedAged, 80 and overCohort StudiesFemaleFinlandHumansMaleMembrane ProteinsMiddle AgedNorwayPrevalenceRegistriesYoung AdultCwh43 protein, mouseMembrane ProteinsCWH43EADBFinnGenFinnishGeneticsNormal pressure hydrocephalusNorwegianOnset ageRisk

Identifiers

PMID39948543
PMCPMC11827454

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