title: A novel de novo Myocilin variant in a patient with sporadic juvenile open angle glaucoma.
abstract: BACKGROUND
  Glaucoma is a leading cause of irreversible blindness. Pathogenic variants in the Myocilin gene (MYOC) cause juvenile open angle glaucoma (JOAG) in 8-36% of cases, and display an autosomal dominant inheritance with high penetrance. Molecular diagnosis is important for early identification as therapies are effective in minimizing vision loss and MYOC variants can be associated to severe glaucoma. MYOC variants are usually inherited, however a fifth of carriers do not report a family history. The occurrence of de novo MYOC variants is currently unknown.
  
  
  METHODS
  In this study we investigated a 14 year old male Caucasian patient diagnosed with JOAG, and no family history of glaucoma. A novel probably deleterious MYOC:p.(Pro254Leu) variant was identified in the index case. This variant was not present in the parents or the siblings.
  
  
  CONCLUSIONS
  This is the second report of a de novo MYOC variant in a sporadic case of JOAG and it is currently unknown if this mechanism occurs more frequently. This finding emphasizes the importance of screening individuals with JOAG for MYOC mutations irrespective of a negative family history.
authors.affiliation: Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, Australia. emmanuelle.souzeau@flinders.edu.au.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Souzeau
authors.affiliation: Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.
authors.forename: Kathryn P
authors.initials: KP
authors.lastname: Burdon
authors.affiliation: Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, Australia.
authors.forename: Bronwyn
authors.initials: B
authors.lastname: Ridge
authors.affiliation: SA Pathology, Flinders Medical Centre, Adelaide, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Dubowsky
authors.affiliation: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye & Ear Hospital, Melbourne, Australia.
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Ruddle
authors.affiliation: Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, Australia.
authors.forename: Jamie E
authors.initials: JE
authors.lastname: Craig
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D005820:Genetic Testing; D014644:Genetic Variation; D005902:Glaucoma, Open-Angle / Q000175:diagnosis / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D044465:White People / Q000235:genetics; D000099179:Myocilin
chemical_list: D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D000099179:Myocilin
keywords: De novo variant; Genetic testing; Glaucoma; Juvenile open angle glaucoma; Myocilin