title: Novel membrane frizzled-related protein gene mutation as cause of posterior microphthalmia resulting in high hyperopia with macular folds.
abstract: OBJECTIVE
  We present a genetic and clinical analysis of two sisters, 3 and 4 years of age, with nanophthalmos and macular folds.
  
  
  METHODS
  Ophthalmological examination, general paediatric examination and molecular genetic analysis of the MFRP gene were performed in both affected siblings.
  
  
  RESULTS
  Clinical analysis showed high hyperopia (+11 D and +12 D), short axial lengths (15 mm) and the presence of macular folds and optic nerve head drusen. Autofluorescence of the retina was generally normal with subtle macular abnormalities. Sequence analysis showed compound heterozygosity for severe MFRP mutations in both sisters: a previously reported p.Asn167fs (c.498dupC) and a novel stop codon mutation p.Gln91X (c.271C>T).
  
  
  CONCLUSIONS
  These are the youngest nanophthalmos patients in the literature identified with severe loss of MFRP function, showing already the known structural abnormalities for this disease. Adult patients affected by homozygous or compound heterozygous MFRP mutations generally show signs of retinal dystrophy, with ERG disturbances and RPE abnormalities on autofluorescence imaging. ERG examination could not be performed in these children, but extensive RPE abnormalities were not seen at this young age.
authors.affiliation: Department of Ophthalmology, University of Groningen, University Medical Center Groningen, Groningen, The NetherlandsDepartment of Clinical Genetics, University of Groningen, University Medical Center Groningen, Groningen, The NetherlandsDepartment of Biomedical Sciences Center of Excellence for Neuroscience, Foster School of Medicine, Texas Tech Health Sciences Center, El Paso, Texas, USA.
authors.forename: Rosemarie A
authors.initials: RA
authors.lastname: Wasmann
authors.forename: Jolien S Klein
authors.initials: JS
authors.lastname: Wassink-Ruiter
authors.forename: Olof H
authors.initials: OH
authors.lastname: Sundin
authors.forename: Elisa
authors.initials: E
authors.lastname: Morales
authors.forename: Joke B G M
authors.initials: JB
authors.lastname: Verheij
authors.forename: Jan Willem R
authors.initials: JW
authors.lastname: Pott
mesh_terms: D002675:Child, Preschool; D004247:DNA / Q000235:genetics*; D015785:Eye Diseases, Hereditary / Q000209:etiology / Q000235:genetics / Q000503:physiopathology*; D005260:Female; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D006956:Hyperopia / Q000209:etiology / Q000235:genetics / Q000503:physiopathology*; D047908:Intracellular Signaling Peptides and Proteins; D008850:Microphthalmos / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D033401:Microscopy, Acoustic; D009154:Mutation; D009898:Optic Disk / Q000473:pathology; D015594:Optic Disk Drusen / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics; D010375:Pedigree; D016133:Polymerase Chain Reaction; D041623:Tomography, Optical Coherence; D000099274:Frizzled-Related Proteins
chemical_list: D004247:DNA; D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; D000099274:Frizzled-Related Proteins
keywords: MFRP; hyperopia; macular folds; membrane frizzled-related protein gene; nanophthalmos