Evidence map›Paper›PMID 40931319›Full record

ArticleClinical genetics2026

LONP1 Variants Are Associated With Clinically Diverse Phenotypes.

Randee E Young, Lu Qiao, Rebecca Hernan, David A Sweetser, Jessica L Waxler, Daryl A Scott, Tiana M Scott, Seema R Lalani, Mahshid S Azamian, Jill A Rosenfeld and 29 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical genetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Molecular mechanisms of mitochondrial AAA+ proteases.The Journal of biological chemistry · 2026
    Review
  2. Beyond the genome: clinical challenges in diagnosingFrontiers in cell and developmental biology · 2026
    Article
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

39 authors.

Randee E YoungDepartment of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Lu QiaoDepartment of Pediatrics, Columbia University Irving Medical Center, New York, New York, USA.
Rebecca HernanDepartment of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
David A SweetserDivision of Medical Genetics and Metabolism, Department of Pediatrics; and Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
Jessica L WaxlerDepartment of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Daryl A ScottDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
Tiana M ScottDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
Seema R LalaniDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
Mahshid S AzamianDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
Jill A RosenfeldDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
Bret BostwickDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
Lindsay C BurrageDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.ORCID 0000-0002-5108-8861
Undiagnosed Diseases Network
Lance H RodanDivision of Genetics and Genomics and Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Bianca E RussellDepartment of Human Genetics, Division of Clinical Genetics, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, California, USA.ORCID 0000-0003-3934-9800
Marina Dutra-ClarkeDepartment of Human Genetics, Division of Clinical Genetics, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
Michael KruerPediatric Movement Disorders Program, Division of Pediatric Neurology, Barrow Neurological Institute, Phoenix Children's Hospital, Phoenix, Arizona, USA.
Somayeh BakhtiarimPediatric Movement Disorders Program, Division of Pediatric Neurology, Barrow Neurological Institute, Phoenix Children's Hospital, Phoenix, Arizona, USA.
Hossein DarvishNeuroscience Research Center, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran.
David J AmorMurdoch Children's Research Institute and University of Melbourne Department of Paediatrics, Royal Children's Hospital, Melbourne, Australia.
Shamima RahmanMitochondrial Research Group, UCL Great Ormond Street Institute of Child Health, and Metabolic Department, Great Ormond Street Hospital for Children, London, UK.
Karen StalsExeter Genomics Laboratory, Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK.
Lisa BradleyDepartment of Clinical Genetics and Department of Neurology, Children's Health Ireland (CHI) at Crumlin, Dublin, Ireland.
Susan ByrneDepartment of Clinical Genetics and Department of Neurology, Children's Health Ireland (CHI) at Crumlin, Dublin, Ireland.
Leandra K TolussoDivision of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Beatrix WongDivision of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Laura BenedictCenter for Human Genetics, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA.
Kimberly WallisCenter for Human Genetics, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA.
Kestutis MickeColorado Fetal Care Center, Children's Hospital Colorado, Aurora, Colorado, USA.
Cindy ColsonUniv. Lille, CHU Lille, ULR7364-RADEME-Maladies RAres du DEveloppement Embryonnaire et du Métabolisme, CRMR Anomalies du Développement et Syndromes Malformatifs, Lille, France.
Thomas SmolUniv. Lille, CHU Lille, ULR7364-RADEME-Maladies RAres du DEveloppement Embryonnaire et du Métabolisme, CRMR Anomalies du Développement et Syndromes Malformatifs, Lille, France.
Sabrina V SouthwickDivision of Maternal Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins Hospital, Baltimore, Maryland, USA.
Kristen A MillerDivision of Maternal Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins Hospital, Baltimore, Maryland, USA.ORCID 0000-0001-8567-3850
Michelle L KushCenter for Fetal Therapy, Department of Gynecology & Obstetrics, Johns Hopkins University, Baltimore, Maryland, USA.
Odelia ChorinInstitute of Rare Diseases, Edmond and Lily Safra Hospital for Children, the Danek Gertner Institute of Genetics, Sheba Medical Center, Ramat Gan, Israel.
Annick RothschildInstitute of Rare Diseases, Edmond and Lily Safra Hospital for Children, the Danek Gertner Institute of Genetics, Sheba Medical Center, Ramat Gan, Israel.
Wei WangGeneDx, LLC, Gaithersburg, Maryland, USA.
Yufeng ShenDepartment of Systems Biology, Columbia University Irving Medical Center, New York, New York, USA.
Wendy K ChungDepartment of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Funding

THE DROSOPHILA GENETICS AND RNAI CORE (THE FLY CORE)P01HD068250 · NICHD · MASSACHUSETTS GENERAL HOSPITAL · PI CHUNG, WENDY K, DONAHOE, PATRICIA K · 2011 to 2022
$17.1M
Genomic analysis of the Multiplex, Autozygous Populations in Cerebral Palsy (MAP CP) cohort: a focused approach to a complex diseaseR01NS127108 · NINDS · UNIVERSITY OF ARIZONA · PI Michael C Kruer · 2023 to 2026
$2.6M
National Institute of Neurological Disorders and Stroke of the National Institutes of Health U01HG007709National Institute of Neurological Disorders and Stroke of the National Institutes of Health U01HG007943NICHD NIH HHS P01 HD068250NIH HHS P01HD068250NINDS NIH HHS R01 NS127108
6 · The paper itself

Abstract

LONP1 encodes a mitochondrial protease essential for protein quality control and metabolism. Variants in LONP1 are associated with a diverse and expanding spectrum of disorders, including Cerebral, Ocular, Dental, Auricular, and Skeletal anomalies syndrome (CODAS), congenital diaphragmatic hernia (CDH), and neurodevelopmental disorders (NDD), with some individuals exhibiting features of mitochondrial encephalopathy. We report 16 novel LONP1 variants identified in 16 individuals (11 with NDD, 5 with CDH), further expanding the clinical spectrum. Structural mapping of disease-associated missense variants revealed phenotype-specific clustering, with CODAS variants enriched in the proteolytic chamber and NDD variants more broadly distributed. CODAS is caused by biallelic variants and CDH by monoallelic variants, both of which are predicted to act through loss-of-function mechanisms. Both monoallelic and biallelic variants are associated with LONP1-related NDD, suggesting complex mechanisms such as dominant-negative effects. Our findings broaden the phenotypic and genetic spectrum of LONP1-associated disorders and highlight the essential role of LONP1 in mitochondrial function and development.

Indexed as

Abnormalities, MultipleATP-Dependent ProteasesGenetic Predisposition to DiseaseMitochondrial ProteinsNeurodevelopmental DisordersAllelesChildChild, PreschoolCraniofacial AbnormalitiesEye AbnormalitiesFemaleGenetic Association StudiesGrowth DisordersHip Dislocation, CongenitalHumansInfantATP-Dependent ProteasesLONP1 protein, humanMitochondrial ProteinsCODAScongenital diaphragmatic herniaLONP1mitochondrial encephalopathyneurodevelopmental disorder

Identifiers

PMID40931319
PMCPMC13261574

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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.