Progression of Phenotype in Leber's Congenital Amaurosis with a Mutation at the LCA5 Locus

Overview

Journal Br J Ophthalmol

Specialty Ophthalmology

Date 2003 Mar 19

PMID 12642313

Citations 11

Authors

M D Mohamed

N C Topping

H Jafri

Y Raashed

M A McKibbin

C F Inglehearn

Affiliations

Soon will be listed here.

Abstract

Background: Leber's congenital amaurosis (LCA) accounts for 5% of inherited retinal disease and is usually inherited as an autosomal recessive trait. Genetic and clinical heterogeneity exist. Mutations have been described in the RPE65, CRB1, RPGRIP1, AIPL1, GUCY2D, and CRX genes and other pedigrees show linkage to the LCA3 and LCA5 loci. The latter is a new locus which maps to 6q11-q16. The ocular findings and the evolution of the macula staphyloma are described in five members of a Pakistani family with consanguinity and a mutation in the LCA5 gene.

Methods: 13 family members including five affected individuals consented to DNA analysis and ocular examination including fundal photography.

Results: Ocular abnormalities are described. The most striking feature was the progression of macula abnormalities in three brothers resulting in a colobomatous appearance in the eldest compared to only mild atrophy in the youngest. The phenotypic pattern of this mutation in this Pakistani family contrasts with the "Old Order River Brethren" who were of Swiss descent, in whom the mutation was first described.

Conclusion: The evolution of a new phenotypic picture is presented to a mutation in LCA5.

Citing Articles

Leber's Congenital Amaurosis: Current Concepts of Genotype-Phenotype Correlations.

Huang C, Yang C, Yang C, Hou Y, Chen T Genes (Basel). 2021; 12(8).

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Voretigene Neparvovec and Gene Therapy for Leber's Congenital Amaurosis: Review of Evidence to Date.

Padhy S, Takkar B, Narayanan R, Venkatesh P, Jalali S Appl Clin Genet. 2020; 13:179-208.

PMID: 33268999 PMC: 7701157. DOI: 10.2147/TACG.S230720.

Treatment Potential for LCA5-Associated Leber Congenital Amaurosis.

Uyhazi K, Aravand P, Bell B, Wei Z, Leo L, Serrano L Invest Ophthalmol Vis Sci. 2020; 61(5):30.

PMID: 32428231 PMC: 7405811. DOI: 10.1167/iovs.61.5.30.

Amelioration of Neurosensory Structure and Function in Animal and Cellular Models of a Congenital Blindness.

Song J, Aravand P, Nikonov S, Leo L, Lyubarsky A, Bennicelli J Mol Ther. 2018; 26(6):1581-1593.

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A mutation in IFT43 causes non-syndromic recessive retinal degeneration.

Biswas P, Duncan J, Ali M, Matsui H, Naeem M, Raghavendra P Hum Mol Genet. 2017; 26(23):4741-4751.

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