Characterisation of severe rod-cone dystrophy in a consanguineous family with a splice site mutation in the MERTK gene

Br J Ophthalmol. 2009 Jul;93(7):920-5. doi: 10.1136/bjo.2008.147397. Epub 2009 Apr 28.

Abstract

Aim: To characterise the ocular phenotype of a family segregating the splice site mutation c.2189+1G>T in the tyrosine kinase receptor gene MERTK.

Methods: Five affected children of a consanguineous Moroccan family were investigated by ophthalmic examinations, including fundus photography, autofluorescence (FAF) imaging, optical coherence tomography (OCT), psychophysical and electrophysiological methods.

Results: Affected children were between 5 and 19 years of age, allowing an estimation of disease progression. Electroretinography demonstrated loss of scotopic and photopic function in the first decade of life. Younger siblings showed drusen-like deposits with focal relatively increased FAF in the macular area. With increasing age, a yellowish lesion with relatively increased FAF and subsequent macular atrophy developed. Visual acuity deteriorated with age and ranged between 20/50 in the best eye of the youngest affected and 20/400 in the worst eye of the oldest affected sibling. Spectral-domain OCT revealed debris-like material in the subneurosensory space.

Conclusion: The splice site mutation c.2189+1G>T in MERTK causes rod-cone dystrophy with a distinct macular phenotype. The debris in the subneurosensory space resembles that in the Royal College of Surgeons (RCS) rat being the mertk animal model. Patients might therefore benefit from advances in gene therapy that were previously achieved in the RCS rat.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Consanguinity
  • DNA Mutational Analysis
  • Female
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Pedigree
  • Phenotype
  • Proto-Oncogene Proteins / genetics*
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Retinitis Pigmentosa / genetics*
  • Retinitis Pigmentosa / physiopathology
  • Tomography, Optical Coherence
  • Visual Fields / physiology
  • Young Adult
  • c-Mer Tyrosine Kinase

Substances

  • Proto-Oncogene Proteins
  • MERTK protein, human
  • Receptor Protein-Tyrosine Kinases
  • c-Mer Tyrosine Kinase