Compound heterozygous novel frameshift variants in the PROM1 gene result in Leber congenital amaurosis
- Sara D. Ragi1,
- Jose Ronaldo Lima de Carvalho Jr.1,2,3,4,
- Akemi J. Tanaka5,
- Karen Sophia Park1,4,
- Vinit B. Mahajan6,
- Irene H. Maumenee1 and
- Stephen H. Tsang1,4,5,7
- 1Department of Ophthalmology, Columbia University, New York, New York 10019, USA;
- 2Department of Ophthalmology, Empresa Brasileira de Servicos Hospitalares (EBSERH)—Hospital das Clinicas de Pernambuco (HCPE), Federal University of Pernambuco (UFPE), Recife, 50670-901 Brazil;
- 3Department of Ophthalmology, Federal University of São Paulo (UNIFESP), São Paulo, 04021-001 Brazil;
- 4Jonas Children's Vision Care and Bernard & Shirlee Brown Glaucoma Laboratory, New York, New York 10019, USA;
- 5Department of Pathology and Cell Biology, Columbia University, New York, New York 10019, USA;
- 6Omics Laboratory, Byers Eye Institute, Stanford University, Palo Alto, California 94303, USA;
- 7Stem Cell Initiative (CSCI), Institute of Human Nutrition, Vagelos College of Physicians and Surgeons, New York, New York 10019, USA
- Corresponding author: sht2{at}cumc.columbia.edu
Abstract
The PROM1 (prominin 1) gene encodes an 865-amino acid glycoprotein that is expressed in retinoblastoma cell lines and in the adult retina. The protein is localized to photoreceptor outer segment disc membranes, where it plays a structural role, and in the retinal pigment epithelium (RPE), where it acts as a cytosolic protein that mediates autophagy. Mutations in PROM1 are typically associated with cone-rod dystrophy 12 (OMIM#3612657), autosomal dominant retinal macular dystrophy 2 (OMIM#608051), autosomal recessive retinitis pigmentosa 41 (OMIM#612095), and Stargardt disease 4 (OMIM#603786). Here we describe the first case of PROM1-associated Leber congenital amaurosis (LCA) in a 12-yr-old Asian male, caused by two not previously described deleterious frameshift variants in the compound heterozygous state. Clinical features include the presence of bull's eye maculopathy, pendular horizontal nystagmus, and photodysphoria consistent with the clinical diagnosis of LCA. The patient was evaluated using ophthalmic imaging, electroretinography, and whole-exome sequencing. Electroretinography revealed extinguished retinal activity.
- Received June 6, 2019.
- Accepted August 14, 2019.
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