September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Molecular study of the MFRP gene in patients with posterior microphthalmia (MCOP) supports its role in autosomal recessive MCOP pathogenesis
Author Affiliations & Notes
  • Basamat Almoallem
    Center for Medical Genetics, Ghent University and Ghent University Hospital, Ghent, Belgium
    Department of Ophthalmology, Ghent University Hospital, Ghent , Belgium
  • Gavin Arno
    Institute of Ophthalmology, University College London, London, United Kingdom
    Department of Ophthalmology, Moorfields Eye Hospital, London, United Kingdom
  • Julie De Zaeytijd
    Department of Ophthalmology, Ghent University Hospital, Ghent , Belgium
  • Sarah Hull
    Institute of Ophthalmology, University College London, London, United Kingdom
    Department of Ophthalmology, Moorfields Eye Hospital, London, United Kingdom
  • Martina Suzani
    Institute of Ophthalmology, University College London, London, United Kingdom
    Department of Ophthalmology, Moorfields Eye Hospital, London, United Kingdom
  • Thomy J. L. de Ravel
    Center for Medical Genetics, University Hospitals of Leuven, Leuven, Belgium
  • Andrew Webster
    Institute of Ophthalmology, University College London, London, United Kingdom
    Department of Ophthalmology, Moorfields Eye Hospital, London, United Kingdom
  • Bart Peter Leroy
    Department of Ophthalmology, Ghent University Hospital, Ghent , Belgium
    Center for Medical Genetics, Ghent University and Ghent University Hospital, Ghent, Belgium
  • Tony Moore
    Institute of Ophthalmology, University College London, London, United Kingdom
    Department of Ophthalmology, Moorfields Eye Hospital, London, United Kingdom
  • Elfride De Baere
    Center for Medical Genetics, Ghent University and Ghent University Hospital, Ghent, Belgium
  • Footnotes
    Commercial Relationships   Basamat Almoallem, None; Gavin Arno, None; Julie De Zaeytijd, None; Sarah Hull, None; Martina Suzani, None; Thomy J. L. de Ravel, None; Andrew Webster, None; Bart Leroy, None; Tony Moore, None; Elfride De Baere, None
  • Footnotes
    Support  Ghent University Special Research Fund (BOF15/GOA/011), Belspo IAP project P7/43 (Belgian Medical Genomics Initiative: BeMGI), Research Foundation - Flanders (FWO) fellowships to B.P.L, E.D.B.
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 6584. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      Basamat Almoallem, Gavin Arno, Julie De Zaeytijd, Sarah Hull, Martina Suzani, Thomy J. L. de Ravel, Andrew Webster, Bart Peter Leroy, Tony Moore, Elfride De Baere; Molecular study of the MFRP gene in patients with posterior microphthalmia (MCOP) supports its role in autosomal recessive MCOP pathogenesis. Invest. Ophthalmol. Vis. Sci. 2016;57(12):6584.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose : Posterior microphthalmia (MCOP) is a rare developmental disease restricted to the posterior segment of the eye. To date, mutations in the MFRP gene, encoding a frizzled-related protein, have been reported in autosomal recessive MCOP (arMCOP), often found in consanguineous families. Here, we aimed to identify the underlying genetic cause of arMCOP in seven unrelated patients from different ethnic origins.

Methods : All patients underwent detailed ophthalmological evaluations and Sanger sequencing of the coding region of MFRP (NM_031433.2). Two patients originating from a consanguineous marriage underwent homozygosity mapping using SNP arrays.

Results : In the patients who underwent homozygosity mapping MFRP was found in a homozygous region of 10.2 and 6.2 Mb respectively. Overall, eight distinct MFRP mutations were found in the patients studied. Five patients were homozygous for an MFRP mutation: two missense variants with predicted pathogenic effect (c.1231T>C p.Y411H, novel; c.1549C>T p.R517W, known) and three frameshift mutations (c.1090_1094del p.T364*, novel; c.498del p.N167T*25 and c.498dup p.N167fs*, known). Moreover, a sixth patient was compound heterozygous for a nonsense mutation (c.955C>T p.Q319*, novel) and novel deletion of 6,2 kb (c.1-6088_54+40delinsA), predicted to abolish the transcription initiation site. The seventh patient was heterozygous for a known frameshift mutation (c.491_492insT p.N167Qfs*34), no second mutation was found so far. All patients had short axial length (13-16.5 mm), reduced visual acuity (0.15-0.8 logMAR) and hyperopia (+13D to +17.25D). Crowded optic discs were noticed in 7/7 and macular folds in 3/7 patients. Optical coherence tomography showed intraretinal cysts in 5/7 patients. Peripheral pigmentary changes were observed in 5/7 patients. Sight threatening complications such as angle closure glaucoma were seen in one patient.

Conclusions : Eight distinct MFRP mutations were identified in all patients studied. Four of these mutations were novel, including a genomic rearrangement, reported here for the first time. No clear genotype-phenotype correlations could be observed. A recent report by Dinculescu et al (2012) suggested that MFRP-associated retinal dystrophy might be a target for gene therapy. The identification of new families with MFRP mutations might offer opportunities for potential gene-based therapies.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×