Progression of phenotype in Leber's congenital amaurosis with a mutation at the LCA5 locus

摘要

BACKGROUND: Leber’s congenital amaurosis (LCA) accounts for 5% of inherited retinal disease and isudusually inherited as an autosomal recessive trait. Genetic and clinical heterogeneity exist. Mutationsudhave been described in the RPE65, CRB1, RPGRIP1, AIPL1, GUCY2D, and CRX genes and other pedigreesudshow linkage to the LCA3 and LCA5 loci. The latter is a new locus which maps to 6q11-q16. Theudocular findings and the evolution of the macula staphyloma are described in five members of a Pakistaniudfamily with consanguinity and a mutation in the LCA5 gene.udududMETHODS: 13 family members including five affected individuals consented to DNA analysis and ocularudexamination including fundal photography.ududRESULTS: Ocular abnormalities are described. The most striking feature was the progression of maculaudabnormalities in three brothers resulting in a colobomatous appearance in the eldest compared to onlyudmild atrophy in the youngest. The phenotypic pattern of this mutation in this Pakistani family contrastsudwith the “Old Order River Brethren” who were of Swiss descent, in whom the mutation was firstuddescribed.udududCONCLUSION: The evolution of a new phenotypic picture is presented to a mutation in LCA5.