The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.
RP1L1 Variants are Associated with a Spectrum of Inherited Retinal Diseases Including Retinitis Pigmentosa and Occult Macular Dystrophy
Article first published online: 17 JAN 2013
© 2012 Wiley Periodicals, Inc.
Volume 34, Issue 3, pages 506–514, March 2013
How to Cite
Davidson, A. E., Sergouniotis, P. I., Mackay, D. S., Wright, G. A., Waseem, N. H., Michaelides, M., Holder, G. E., Robson, A. G., Moore, A. T., Plagnol, V. and Webster, A. R. (2013), RP1L1 Variants are Associated with a Spectrum of Inherited Retinal Diseases Including Retinitis Pigmentosa and Occult Macular Dystrophy. Hum. Mutat., 34: 506–514. doi: 10.1002/humu.22264
Communicated by Daniel F. Schorderet
Contract grant sponsors: RP Fighting Blindness (formerly British Retinitis Pigmentosa Society); Moorfields Eye Hospital Special Trustees; Fight for Sight (Mercer Fund); National Institute for Health Research UK (Moorfields Eye Hospital and Institute of Ophthalmology Biomedical Research Centre, London, UK); the Foundation Fighting Blindness (USA); UK Medical Research Council (G1001158); Macular Disease Society UK.
- Issue published online: 18 FEB 2013
- Article first published online: 17 JAN 2013
- Accepted manuscript online: 21 DEC 2012 06:05AM EST
- Manuscript Accepted: 5 DEC 2012
- Manuscript Received: 21 SEP 2012
- RP Fighting Blindness (formerly British Retinitis Pigmentosa Society)
- Moorfields Eye Hospital Special Trustees
- Fight for Sight (Mercer Fund)
- National Institute for Health Research UK (Moorfields Eye Hospital and Institute of Ophthalmology Biomedical Research Centre, London, UK)
- the Foundation Fighting Blindness (USA)
- UK Medical Research Council. Grant Number: G1001158
- Macular Disease Society UK
- retinitis pigmentosa 1-like1;
- retinitis pigmentosa;
- occult macular dystrophy;
- retinal disease;
- exome sequencing
In one consanguineous family with retinitis pigmentosa (RP), a condition characterized by progressive visual loss due to retinal degeneration, homozygosity mapping, and candidate gene sequencing suggested a novel locus. Exome sequencing identified a homozygous frameshifting mutation, c.601delG, p.Lys203Argfs*28, in RP1L1 encoding RP 1-like1, a photoreceptor-specific protein. A screen of a further 285 unrelated individuals with autosomal recessive RP identified an additional proband, homozygous for a missense variant, c.1637G>C, p.Ser546Thr, in RP1L1. A distinct retinal disorder, occult macular dystrophy (OCMD) solely affects the central retinal cone photoreceptors and has previously been reported to be associated with variants in the same gene. The association between mutations in RP1L1 and the disorder OCMD was explored by screening a cohort of 28 unrelated individuals with the condition; 10 were found to harbor rare (minor allele frequency ≤0.5% in the 1,000 genomes dataset) heterozygous RP1L1 missense variants. Analysis of family members revealed many unaffected relatives harboring the same variant. Linkage analysis excluded the possibility of a recessive mode of inheritance, and sequencing of RP1, a photoreceptor protein that interacts with RP1L1, excluded a digenic mechanism involving this gene. These findings imply an important and diverse role for RP1L1 in human retinal physiology and disease.