Late-onset pattern macular dystrophy mimicking ABCA4 and PRPH2 disease is caused by a homozygous frameshift mutation in ROM1
- Chu Jian Ma1,
- Winston Lee1,
- Nicholas Stong2,
- Jana Zernant1,
- Stanley Chang1,
- David Goldstein2,
- Takayuki Nagasaki1 and
- Rando Allikmets1,3
- 1Department of Ophthalmology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA;
- 2Institute of Genomic Medicine, Columbia University, New York, New York 10032, USA;
- 3Department of Pathology and Cell Biology, Columbia University, New York, New York 10032, USA
- Corresponding author: rla22{at}cumc.columbia.edu
Abstract
ROM1 (retinal outer segment membrane protein 1) is a 351-amino acid integral membrane protein on Chromosome 11q, with high structural similarity to PRPH2/RDS. Localized at the rims of photoreceptor outer segments (OSs), it is required for the maintenance of OS structure. Here, we describe a case with a phenotypic manifestation of a homozygous single-base pair deletion, c.712delC (p.Leu238Cysfs*78) in the ROM1 gene, resulting in early termination at exon 2. The variant was detected by whole-exome sequencing (WES) in a 63-yr-old Caucasian woman with late-onset pattern macular dystrophy. Notably, although the phenotype resembles those caused by pathogenic variants in ABCA4 or RDS/PRPH2, no pathogenic variants in these, or any other plausible candidate genes, were identified by WES. Clinical features include the presence of hyperautofluorescent flecks, relative sparing of the central macula, and preserved visual acuity. Reduced visual sensitivity was detected among flecked regions in the retina; however, full-field electroretinogram testing revealed no generalized cone dysfunction. The described first case of the complete loss of ROM1 protein function in the retina suggests its sufficiency for late-onset macular dystrophy. ROM1 and PRPH2 pattern macular dystrophies exhibit phenotype overlap, which may be attributable to their shared role in maintenance of the photoreceptor outer segment structure.
Footnotes
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[Supplemental material is available for this article.]
- Received November 7, 2018.
- Accepted December 27, 2018.
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