title: High myopia-excavated optic disc anomaly associated with a frameshift mutation in the MYC-binding protein 2 gene (MYCBP2).
abstract: OBJECTIVE
  To investigate the ocular and neurologic manifestations, and to identify the causative mutation in a family with an excavated optic disc anomaly, high myopia, enlarged axial lengths, and abnormal visual evoked response (VER).
  
  
  METHODS
  Prospective observational case series with whole exome sequencing.
  
  
  METHODS
  Institutional study of 8 family members from 3 generations. Clinical examination included visual field examination, optical coherence tomography, axial length measurement, audiometry, visual evoked response (VER), orbital and cerebral magnetic resonance imaging (MRI), and renal ultrasound. DNA was analyzed by whole exome sequencing and Sanger sequencing. Main outcome measures were clinical and radiological findings, and DNA sequence data.
  
  
  RESULTS
  Three affected family members, a father and his 2 daughters, were examined. The parents and siblings of the father were healthy. Affected individuals presented with excavated optic discs, high myopia (-1.00 to -16.00 diopters), and increased axial lengths. Reduced visual acuity (0.05-0.8) and decreased sensitivity on visual field examination were observed. VER revealed prolonged latency times. Affected eyes appeared ovoid on MRI and the father had thin optic nerves. Exome sequencing revealed that the father was heterozygous for a de novo 5 bp deletion in MYCBP2, c.5906_5910del; p.Glu1969Valfs*26. The same mutation was found in his 2 affected daughters, but not in his parents or siblings, or in public databases.
  
  
  CONCLUSIONS
  We describe a distinct excavated optic disc anomaly associated with high myopia and increased axial length. The condition appears to follow an autosomal dominant pattern and segregate with a deletion in MYCBP2. We suggest naming this entity high myopia-excavated optic disc anomaly.
authors: Department of Ophthalmology, Haukeland University Hospital, Bergen, Norway; Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
authors: Cecilie
authors: C
authors: Bredrup
authors: Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway.
authors: Stefan
authors: S
authors: Johansson
authors: Department of Neurology, Haukeland University Hospital, Bergen, Norway; Department of Clinical Medicine, University of Bergen, Bergen, Norway.
authors: Laurence A
authors: LA
authors: Bindoff
authors: Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway; Computational Biology Unit, Department of Informatics, University of Bergen, Bergen, Norway.
authors: Pawel
authors: P
authors: Sztromwasser
authors: Department of Radiology, Haukeland University Hospital, Bergen, Norway.
authors: Jostein
authors: J
authors: Kråkenes
authors: Department of Ophthalmology, Haukeland University Hospital, Bergen, Norway; Department of Clinical Medicine, University of Bergen, Bergen, Norway.
authors: Anne E C
authors: AE
authors: Mellgren
authors: Department of Radiology, Haukeland University Hospital, Bergen, Norway.
authors: Kari R
authors: KR
authors: Brurås
authors: Department of Otolaryngology-Head and Neck Surgery, Haukeland University Hospital, Bergen, Norway.
authors: Ola
authors: O
authors: Lind
authors: Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway.
authors: Helge
authors: H
authors: Boman
authors: Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway.
authors: Per M
authors: PM
authors: Knappskog
authors: Department of Ophthalmology, Haukeland University Hospital, Bergen, Norway; Department of Clinical Medicine, University of Bergen, Bergen, Norway. Electronic address: eyvind.rodahl@helse-bergen.no.
authors: Eyvind
authors: E
authors: Rødahl
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000293:Adolescent; D058452:Axial Length, Eye / Q000473:pathology; D002648:Child; D005074:Evoked Potentials, Visual; D059472:Exome / Q000235:genetics; D005124:Eye Abnormalities / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics*; D060005:Genotyping Techniques; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D047728:Myopia, Degenerative / Q000235:genetics* / Q000503:physiopathology; D009898:Optic Disk / Q000002:abnormalities*; D010375:Pedigree; D011446:Prospective Studies; D041623:Tomography, Optical Coherence; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D014792:Visual Acuity / Q000502:physiology; D014794:Visual Fields / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C114022:MYCBP2 protein, human; D044767:Ubiquitin-Protein Ligases