ArticleJournal of medical genetics2016
Identification of biallelic LRRK1 mutations in osteosclerotic metaphyseal dysplasia and evidence for locus heterogeneity.
Article in Journal of medical genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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.
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Who cites it
32 citing papers in PubMed, 47 citations in OpenAlex.
- LRRK2: Molecular Mechanisms in Parkinson's Disease.International journal of molecular sciences · 2026Review
- Expression of Phosphomimetic OSTM1-T328E/S329D Variant Partially Restores Bone Resorption Defect in LRRK1-Deficient Mice.Biology · 2026Article
- Beyond resorption: targeting osteoclast fusion and polarization to restore balanced bone remodeling.Frontiers in pharmacology · 2026Review
- Genome-wide association study and genomic selection for growth-related traits in Eastern oyster (Crassostrea virginica).BMC genomics · 2025Article
- Type II kinase inhibitors that target Parkinson's disease-associated LRRK2.Science advances · 2025Article
- Identification of genetic variants associated with clinical features of sickle cell disease.Scientific reports · 2024Article
- Osteosclerotic Metaphyseal Dysplasia Due to a Likely Pathogenic LRRK1 Variant as a Cause of Recurrent Long Bone Fractures.JBMR plus · 2023Article
- Leucine Repeat Rich Kinase 1 Controls Osteoclast Activity by Managing Lysosomal Trafficking and Secretion.Biology · 2023Article
- Skeletal phenotypes in secreted frizzled-related protein 4 gene knockout mice mimic skeletal architectural abnormalities in subjects with Pyle's disease from SFRP4 mutations.Bone research · 2023Article
- Case Report: Osteosclerotic metaphyseal dysplasia with optic nerve involvement and progressive osteonecrosis of the jaw due to a novel LRRK1 mutation.Frontiers in endocrinology · 2023Article
- Dysosteosclerosis: Clinical and Radiological Evolution Reflecting Genetic Heterogeneity.JBMR plus · 2022Article
- Osteosclerotic metaphyseal dysplasia, dysosteosclerosis or osteomyelitis? Paediatric case presentation with associated mandibular swelling and a review of the literature.BMJ case reports · 2022Article
- Positive Selection and Enhancer Evolution Shaped Lifespan and Body Mass in Great Apes.Molecular biology and evolution · 2022Article
- Modelling the functional genomics of Parkinson's disease in Caenorhabditis elegans: LRRK2 and beyond.Bioscience reports · 2021Review
- Germline Saturation Mutagenesis Induces Skeletal Phenotypes in Mice.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2021Article
- Autosomal recessive osteopetrosis: mechanisms and treatments.Disease models & mechanisms · 2021Review
- Deciphering the LRRK code: LRRK1 and LRRK2 phosphorylate distinct Rab proteins and are regulated by diverse mechanisms.The Biochemical journal · 2021Article
- Chemical IN04 Inhibits the Kinase Domain not the ROC Domain of LRRK1: Results from Homology Modeling and Molecular Docking.Medicinal chemistry (Shariqah (United Arab Emirates)) · 2021Article
- Whole exome sequencing in ADHD trios from single and multi-incident families implicates new candidate genes and highlights polygenic transmission.European journal of human genetics : EJHG · 2020Article
- Novel Role for Claudin-11 in the Regulation of Osteoblasts via Modulation of ADAM10-Mediated Notch Signaling.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2019Article
Corrections and comments
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Authors and funding
16 authors at 14 institutions in 5 countries.
Funding
Abstract
backgroundOsteosclerotic metaphyseal dysplasia (OSMD) is a unique form of osteopetrosis characterised by severe osteosclerosis localised to the bone ends. The mode of inheritance is autosomal recessive. Its genetic basis is not known.
objectiveTo identify the disease gene for OSMD. METHODS AND
resultsBy whole exome sequencing in a boy with OSMD, we identified a homozygous 7 bp deletion (c.5938_5944delGAGTGGT) in the LRRK1 gene. His skeletal phenotype recapitulated that seen in the Lrrk1-deficient mouse. The shared skeletal hallmarks included severe sclerosis in the undermodelled metaphyses and epiphyseal margins of the tubular bones, costal ends, vertebral endplates and margins of the flat bones. The deletion is predicted to result in an elongated LRRK1 protein (p.E1980Afs*66) that lacks a part of its WD40 domains. In vitro functional studies using osteoclasts from Lrrk1-deficient mice showed that the deletion was a loss of function mutation. Genetic analysis of LRRK1 in two unrelated patients with OSMD suggested that OSMD is a genetically heterogeneous condition.
conclusionsThis is the first study to identify the causative gene of OSMD. Our study provides evidence that LRRK1 plays a critical role in the regulation of bone mass in humans.
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