ArticlePLoS genetics2011
Loss of the BMP antagonist, SMOC-1, causes Ophthalmo-acromelic (Waardenburg Anophthalmia) syndrome in humans and mice.
Article in PLoS genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 48 papers, 1 of them a synthesis that pooled it.
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Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 citations in OpenAlex.
- Genome-wide association study identifies nine novel loci for 2D:4D finger ratio, a putative retrospective biomarker of testosterone exposure in utero.Human molecular genetics · 2018Pooled it
- Genetic association suggests that SMOC1 mediates between prenatal sex hormones and digit ratio.Human genetics · 2013Trial
- Subepithelial myofibroblasts enhance stem cell regeneration after intestinal epithelial damage.Development (Cambridge, England) · 2026Article
- Characterization of Ocular Developmental Disorders in the Israeli Population: Genotype-Phenotype Correlations and Novel Candidate Genes.Biomolecules · 2026Article
- Autocrine ECM molecules establish MSC quiescence during incisor development by disrupting WNT ligand trafficking process.Nature communications · 2025Article
- Genotypic and phenotypic spectrum of anophthalmia/microphthalmia in families from Khyber Pakhtunkhwa, Pakistan.Journal of human genetics · 2025Article
- SMOC1 colocalizes with Alzheimer's disease neuropathology and delays Aβ aggregation.Acta neuropathologica · 2024Article
- SMOC1 colocalizes with Alzheimer's disease neuropathology and delays Aβ aggregation.Research square · 2024Article
- Downregulation of SMOC1 is associated with progression of colorectal traditional serrated adenomas.BMC gastroenterology · 2024Article
- Why do humans need thrombospondin-1?Journal of cell communication and signaling · 2023Review
- SMOC-1 interacts with both BMP and glypican to regulate BMP signaling in C. elegans.PLoS biology · 2023Article
- Article
- SPARC-related modular calcium binding 1 regulates aortic valve calcification by disrupting BMPR-II/p-p38 signalling.Cardiovascular research · 2022Article
- Smoc1 and Smoc2 regulate bone formation as downstream molecules of Runx2.Communications biology · 2021Article
- Differential intolerance to loss of function and missense mutations in genes that encode human matricellular proteins.Journal of cell communication and signaling · 2021Article
- Maternal H3K27me3-dependent autosomal and X chromosome imprinting.Nature reviews. Genetics · 2020Review
- Review
- The Use of Induced Pluripotent Stem Cells as a Model for Developmental Eye Disorders.Frontiers in cellular neuroscience · 2020Article
- Sostdc1 is expressed in all major compartments of developing and adult mammalian eyes.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2019Article
- Secreted modular calcium-binding proteins in pathophysiological processes and embryonic development.Chinese medical journal · 2019Review
Corrections and comments
- Erratum issued
Authors and funding
36 authors at 18 institutions in 9 countries.
Funding
Abstract
Ophthalmo-acromelic syndrome (OAS), also known as Waardenburg Anophthalmia syndrome, is defined by the combination of eye malformations, most commonly bilateral anophthalmia, with post-axial oligosyndactyly. Homozygosity mapping and subsequent targeted mutation analysis of a locus on 14q24.2 identified homozygous mutations in SMOC1 (SPARC-related modular calcium binding 1) in eight unrelated families. Four of these mutations are nonsense, two frame-shift, and two missense. The missense mutations are both in the second Thyroglobulin Type-1 (Tg1) domain of the protein. The orthologous gene in the mouse, Smoc1, shows site- and stage-specific expression during eye, limb, craniofacial, and somite development. We also report a targeted pre-conditional gene-trap mutation of Smoc1 (Smoc1(tm1a)) that reduces mRNA to ∼10% of wild-type levels. This gene-trap results in highly penetrant hindlimb post-axial oligosyndactyly in homozygous mutant animals (Smoc1(tm1a/tm1a)). Eye malformations, most commonly coloboma, and cleft palate occur in a significant proportion of Smoc1(tm1a/tm1a) embryos and pups. Thus partial loss of Smoc-1 results in a convincing phenocopy of the human disease. SMOC-1 is one of the two mammalian paralogs of Drosophila Pentagone, an inhibitor of decapentaplegic. The orthologous gene in Xenopus laevis, Smoc-1, also functions as a Bone Morphogenic Protein (BMP) antagonist in early embryogenesis. Loss of BMP antagonism during mammalian development provides a plausible explanation for both the limb and eye phenotype in humans and mice.
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Registered trials
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.