ArticlePLoS genetics2017
Mutations in HYAL2, Encoding Hyaluronidase 2, Cause a Syndrome of Orofacial Clefting and Cor Triatriatum Sinister in Humans and Mice.
Article in PLoS genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Genome-wide meta-analyses identify five new risk loci for nonsyndromic orofacial clefts in the Chinese Han population.Molecular genetics & genomic medicine · 2023Pooled it
- Molecular interplay between sperm and oocyte: a narrative review.Human reproduction update · 2026Review
- Anatomical and electrophysiological characteristics of the intra-atrial membranous structure in a patient with cor triatriatum sinister undergoing atrial fibrillation catheter ablation.HeartRhythm case reports · 2026Article
- [The cochlear extracellular matrix gene mutations and hearing loss].Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery · 2025Review
- Hyaluronidase 2 deficiency due to novel compound heterozygous variants in HYAL2: a case report of siblings with HYAL2 deficiency showing different clinical severity and literature review.Journal of human genetics · 2025Review
- Extracellular matrix in vascular homeostasis and disease.Nature reviews. Cardiology · 2025Review
- Limiting extracellular matrix expansion in diet-induced obese mice reduces cardiac insulin resistance and prevents myocardial remodelling.Molecular metabolism · 2024Article
- Genetic Deficiencies of Hyaluronan Degradation.Cells · 2024Review
- Extracellular matrix remodelling in obesity and metabolic disorders.Life metabolism · 2023Article
- Cor Triatriatum Sinister Presenting as Cardioembolic Stroke in a Young Woman.Diagnostics (Basel, Switzerland) · 2022Article
- Elucidating the clinical spectrum and molecular basis of HYAL2 deficiency.Genetics in medicine : official journal of the American College of Medical Genetics · 2022Article
- Hyaluronidases in Human Diseases.International journal of molecular sciences · 2021Review
- Hyaluronidase-2 Regulates RhoA Signaling, Myofibroblast Contractility, and Other Key Profibrotic Myofibroblast Functions.The American journal of pathology · 2020Article
- TMEM2: A missing link in hyaluronan catabolism identified?Matrix biology : journal of the International Society for Matrix Biology · 2019Review
- Comparative analysis of avian hearts provides little evidence for variation among species with acquired endothermy.Journal of morphology · 2019Article
- Hyaluronidase 2 Deficiency Causes Increased Mesenchymal Cells, Congenital Heart Defects, and Heart Failure.Circulation. Cardiovascular genetics · 2017Article
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Authors and funding
24 authors at 12 institutions in 4 countries.
Funding
Abstract
Orofacial clefting is amongst the most common of birth defects, with both genetic and environmental components. Although numerous studies have been undertaken to investigate the complexities of the genetic etiology of this heterogeneous condition, this factor remains incompletely understood. Here, we describe mutations in the HYAL2 gene as a cause of syndromic orofacial clefting. HYAL2, encoding hyaluronidase 2, degrades extracellular hyaluronan, a critical component of the developing heart and palatal shelf matrix. Transfection assays demonstrated that the gene mutations destabilize the molecule, dramatically reducing HYAL2 protein levels. Consistent with the clinical presentation in affected individuals, investigations of Hyal2-/- mice revealed craniofacial abnormalities, including submucosal cleft palate. In addition, cor triatriatum sinister and hearing loss, identified in a proportion of Hyal2-/- mice, were also found as incompletely penetrant features in affected humans. Taken together our findings identify a new genetic cause of orofacial clefting in humans and mice, and define the first molecular cause of human cor triatriatum sinister, illustrating the fundamental importance of HYAL2 and hyaluronan turnover for normal human and mouse development.
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Registered trials
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