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

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.

• Authors: Sara D Ragi, Jose Ronaldo Lima de Carvalho Jr, Akemi J Tanaka, Karen Sophia Park, Vinit B Mahajan, Irene H Maumenee, Stephen H Tsang
• Journal: Cold Spring Harbor molecular case studies (Cold Spring Harb Mol Case Stud) Vol. 5 Issue 6 (12 2019) ISSN: 2373-2873 [Electronic] United States
• PMID: 31836589 (Publication Type: Case Reports, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © 2019 Ragi et al.; Published by Cold Spring Harbor Laboratory Press.

Chemical References

• AC133 Antigen
• PROM1 protein, human

Topics

• AC133 Antigen (genetics, metabolism)
• Adult
• Child
• Electroretinography
• Family
• Female
• Frameshift Mutation (genetics)
• Heterozygote
• Humans
• Leber Congenital Amaurosis (genetics, metabolism)
• Male
• Mutation (genetics)
• Pedigree
• Phenotype
• Retina
• Retinitis Pigmentosa
• Exome Sequencing