Clinicopathologic effects of mutant GUCY2D in Leber congenital amaurosis

Ann H Milam; Mark R Barakat; Nisha Gupta; Linda Rose; Tomas S Aleman; Michael J Pianta; Artur V Cideciyan; Val C Sheffield; Edwin M Stone; Samuel G Jacobson

doi:10.1016/S0161-6420(02)01757-8

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Clinicopathologic effects of mutant GUCY2D in Leber congenital amaurosis

Journal article

Peer reviewed

Clinicopathologic effects of mutant GUCY2D in Leber congenital amaurosis

Ann H Milam, Mark R Barakat, Nisha Gupta, Linda Rose, Tomas S Aleman, Michael J Pianta, Artur V Cideciyan, Val C Sheffield, Edwin M Stone and Samuel G Jacobson

Ophthalmology (Rochester, Minn.), Vol.110(3), pp.549-558

03/2003

DOI: 10.1016/S0161-6420(02)01757-8

PMID: 12623820

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Abstract

To study the retinal degeneration in an 11 -year-old patient with Leber congenital amaurosis (LCA) caused by mutation in GUCY2D. Comparative human tissue study. Two subjects with LCA; postmortem eye from one LCA patient and three normal donors. Clinical and visual function studies were performed between the ages of 6 and 10 years in the LCA eye donor and at age 6 in an affected sibling. Genomic DNA was screened for mutations in known LCA genes. The retina of the 11 -year-old subject with LCA was compared with normal retinas from donors age 3 days, 18 years, and 53 years. The tissues were processed for histopathologic studies and immunofluorescence with retinal cell-specific antibodies. Vision in both siblings at the ages examined was limited to severely impaired cone function. Mutation in the GUCY2D gene was identified in both siblings. Histopathologic study revealed rods and cones without outer segments in the macula and far periphery. The cones formed a monolayer of cell bodies, but the rods were clustered and had sprouted neurites in the periphery. Rods and cones were not identified in the midperipheral retina. The inner nuclear layer appeared normal in thickness throughout the retina, but ganglion cells were reduced in number. An 11-year-old subject with LCA caused by mutant GUCY2D had only light perception but retained substantial numbers of cones and rods in the macula and far periphery. The finding of numerous photoreceptors at this age may portend well for therapies designed to restore vision at the photoreceptor level.

Electroretinography

Retinal Degeneration - genetics

Humans

Middle Aged

Genotype

Optic Atrophy, Hereditary, Leber - genetics

Visual Acuity

Polymorphism, Single-Stranded Conformational

Optic Atrophy, Hereditary, Leber - pathology

Optic Atrophy, Hereditary, Leber - enzymology

DNA Mutational Analysis

Pedigree

Visual Fields

Adolescent

Female

Guanylate Cyclase - genetics

Blindness - congenital

Mutation

Retinal Degeneration - pathology

Child

Photoreceptor Cells, Vertebrate - pathology

Retinal Degeneration - enzymology

Fluorescent Antibody Technique, Indirect

Infant, Newborn

Details

Title: Subtitle: Clinicopathologic effects of mutant GUCY2D in Leber congenital amaurosis
Creators: Ann H Milam - Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania School of Medicine, 51 North 39th Street, Philadelphia, PA 19104, USA
Mark R Barakat
Nisha Gupta
Linda Rose
Tomas S Aleman
Michael J Pianta
Artur V Cideciyan
Val C Sheffield
Edwin M Stone
Samuel G Jacobson
Resource Type: Journal article
Publication Details: Ophthalmology (Rochester, Minn.), Vol.110(3), pp.549-558
DOI: 10.1016/S0161-6420(02)01757-8
PMID: 12623820
NLM abbreviation: Ophthalmology
ISSN: 0161-6420
eISSN: 1549-4713
Publisher: United States
Grant note: EY 05627 / NEI NIH HHS EY 13203 / NEI NIH HHS EY 13385 / NEI NIH HHS EY 13729 / NEI NIH HHS
Language: English
Date published: 03/2003
Academic Unit: Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Ophthalmology and Visual Sciences
Record Identifier: 9983980084402771

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