Evidence map›Paper›PMID 40133303›Full record

ArticleNPJ genomic medicine2025

Pathogenic SMAD6 variants in patients with idiopathic and complex congenital heart disease associated pulmonary arterial hypertension.

Sofia Karl, Ekkehard Grünig, Memoona Shaukat, Matthias Held, Christian Apitz, Fabian von Scheidt, Ralf Geiger, Michael Halank, Karen M Olsson, Marius M Hoeper and 11 more

Abstract read
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In one paragraph

Article in NPJ genomic medicine, 2025. 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

21 authors.

Sofia KarlCenter for Pulmonary Hypertension, Thoraxklinik Heidelberg gGmbH at Heidelberg University Hospital and Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), Heidelberg, Germany.
Ekkehard GrünigCenter for Pulmonary Hypertension, Thoraxklinik Heidelberg gGmbH at Heidelberg University Hospital and Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), Heidelberg, Germany.
Memoona ShaukatCenter for Pulmonary Hypertension, Thoraxklinik Heidelberg gGmbH at Heidelberg University Hospital and Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), Heidelberg, Germany.
Matthias HeldDepartment of Pulmonary Medicine, KWM Missio Clinic, Würzburg, Germany.ORCID http://orcid.org/0000-0002-5855-7667
Christian ApitzDepartment for Pediatric Cardiology, University Hospital Ulm, Ulm, Germany.
Fabian von ScheidtDepartment of Congenital Heart Disease and Pediatric Cardiology, German Heart Center Munich, Munich, Germany.
Ralf GeigerPediatrics III (Cardiopulmonary Unit), Department of Child and Adolescent Health, Medical University Innsbruck, Innsbruck, Austria.
Michael HalankDevision of Pulmonology, Medical Department I, University Hospital Carl Gustav Carus of TU Dresden, Dresden, Germany.
Karen M OlssonDepartment of Respiratory Medicine and Infectious Diseases, Hannover Medical School, Hannover and Biomedical Research in Endstage and Obstructive Lung Disease Hanover (BREATH), German Center for Lung Research (DZL), Hannover, Germany.
Marius M HoeperDepartment of Respiratory Medicine and Infectious Diseases, Hannover Medical School, Hannover and Biomedical Research in Endstage and Obstructive Lung Disease Hanover (BREATH), German Center for Lung Research (DZL), Hannover, Germany.
Jan C KampDepartment of Respiratory Medicine and Infectious Diseases, Hannover Medical School, Hannover and Biomedical Research in Endstage and Obstructive Lung Disease Hanover (BREATH), German Center for Lung Research (DZL), Hannover, Germany.
Gabor KovacsDivision of Pulmonology, Department of Internal Medicine, Medical University of Graz and Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria.
Horst OlschewskiDivision of Pulmonology, Department of Internal Medicine, Medical University of Graz and Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria.ORCID http://orcid.org/0000-0002-2834-7466
Hans-Jürgen SeyfarthDepartment of Pneumology, Medical Clinic II, University Hospital of Leipzig, Leipzig, Germany.
Katrin MilgerDepartment of Internal Medicine V, Ludwig-Maximilian University of Munich; Asklepios Clinic Gauting, Comprehensive Pneumology Centre Munich (CPC), German Center for Lung Research (DZL), Munich, Germany.
Ralf EwertDepartment of Internal Medicine B-Cardiology, Intensive Care, Pulmonary Medicine and Infectious Diseases, University of Greifswald, Greifswald, Germany.
Hans KloseDepartment of Pneumology, Department of Medicine II, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Benjamin EgenlaufCenter for Pulmonary Hypertension, Thoraxklinik Heidelberg gGmbH at Heidelberg University Hospital and Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), Heidelberg, Germany.
Panagiota XanthouliCenter for Pulmonary Hypertension, Thoraxklinik Heidelberg gGmbH at Heidelberg University Hospital and Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), Heidelberg, Germany.
Katrin HinderhoferLaboratory for Molecular Genetic Diagnostics, Institute of Human Genetics, Heidelberg University, Heidelberg, Germany.
Christina A EichstaedtCenter for Pulmonary Hypertension, Thoraxklinik Heidelberg gGmbH at Heidelberg University Hospital and Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), Heidelberg, Germany. christina.eichstaedt@med.uni-heidelberg.de.ORCID http://orcid.org/0000-0001-7288-8297

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In patients with complex congenital heart disease (CHD) pathogenic SMAD6 variants have been described previously. The aim of this study was to analyze if pathogenic SMAD6 variants also occur in patients with CHD associated with pulmonary arterial hypertension (CHD-APAH) or idiopathic PAH. A PAH gene panel with up to 64 genes including SMAD6 was used to sequence 311 patients with idiopathic PAH (IPAH) and 32 with CHD-APAH. In 4 of 32 (12.5%) CHD-APAH and in 2 out of 311 (0.64%) IPAH patients we identified likely pathogenic or rare SMAD6 missense variants. All CHD-APAH patients with a rare SMAD6 variant had complex CHD. One patient had bi-allelic SMAD6 variants, combined pulmonary valve defect and supravalvular aortic stenosis, craniosynostosis and radioulnar synostosis. This is the first description of potentially disease-causing SMAD6 variants in patients with IPAH and complex CHD-APAH. Further studies are needed to assess pathogenesis and prevalence of pathogenic SMAD6 variants in PAH.

Identifiers

PMID40133303
PMCPMC11937313

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