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Cold Spring Harb Mol Case Stud. 2019 Dec 13;5(6). pii: a004481. doi: 10.1101/mcs.a004481. Print 2019 Dec.

Compound heterozygous novel frameshift variants in the PROM1 gene result in Leber congenital amaurosis.

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Department of Ophthalmology, Columbia University, New York, New York 10019, USA.
Department of Ophthalmology, Empresa Brasileira de Servicos Hospitalares (EBSERH)-Hospital das Clinicas de Pernambuco (HCPE), Federal University of Pernambuco (UFPE), Recife, 50670-901 Brazil.
Department of Ophthalmology, Federal University of São Paulo (UNIFESP), São Paulo, 04021-001 Brazil.
Jonas Children's Vision Care and Bernard & Shirlee Brown Glaucoma Laboratory, New York, New York 10019, USA.
Department of Pathology and Cell Biology, Columbia University, New York, New York 10019, USA.
Omics Laboratory, Byers Eye Institute, Stanford University, Palo Alto, California 94303, USA.
Stem Cell Initiative (CSCI), Institute of Human Nutrition, Vagelos College of Physicians and Surgeons, New York, New York 10019, USA.


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.


congenital horizontal nystagmus; congenital visual impairment; severe visual impairment

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