14 research outputs found
Cardiovascular Genetics: Case Studies
What I\u27d like to do in the next 10 or 15 minutes is use a case approach which we all use in medicine as you use in law to give you a flavor for how we as clinicians think about things that are oftentimes obviously genetic. But I want to stress to you that probably a day does not go by or a patient does not go by where I don\u27t think in terms of genetic issues for their cardiovascular health
Cardiovascular Genetics: Case Studies
What I\u27d like to do in the next 10 or 15 minutes is use a case approach which we all use in medicine as you use in law to give you a flavor for how we as clinicians think about things that are oftentimes obviously genetic. But I want to stress to you that probably a day does not go by or a patient does not go by where I don\u27t think in terms of genetic issues for their cardiovascular health
Mutations in HYAL2, Encoding Hyaluronidase 2, Cause a Syndrome of Orofacial Clefting and Cor Triatriatum Sinister in Humans and Mice.
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