Novel membrane frizzled-related protein gene mutation as cause of posterior microphthalmia resulting in high hyperopia with macular folds

Acta Ophthalmol. 2014 May;92(3):276-81. doi: 10.1111/aos.12105. Epub 2013 Jun 7.

Abstract

Purpose: 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).

Conclusion: 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.

Keywords: MFRP; hyperopia; macular folds; membrane frizzled-related protein gene; nanophthalmos.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural

MeSH terms

  • Child, Preschool
  • DNA / genetics*
  • Eye Diseases, Hereditary / etiology
  • Eye Diseases, Hereditary / genetics
  • Eye Diseases, Hereditary / physiopathology*
  • Female
  • Glycoproteins / genetics*
  • Glycoproteins / metabolism
  • Heterozygote
  • Humans
  • Hyperopia / etiology
  • Hyperopia / genetics
  • Hyperopia / physiopathology*
  • Intracellular Signaling Peptides and Proteins
  • Microphthalmos / complications
  • Microphthalmos / genetics*
  • Microphthalmos / metabolism
  • Microscopy, Acoustic
  • Mutation*
  • Optic Disk / pathology
  • Optic Disk Drusen / diagnosis
  • Optic Disk Drusen / etiology*
  • Optic Disk Drusen / genetics
  • Pedigree
  • Polymerase Chain Reaction
  • Tomography, Optical Coherence

Substances

  • Glycoproteins
  • Intracellular Signaling Peptides and Proteins
  • WD repeat containing planar cell polarity effector
  • DNA

Supplementary concepts

  • Hyperopia, High