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MD Mohamed, MA McKibbin, H Jafri, Y Raashed, CF Inglehearn; New Pedigrees Linking to the LCA5 Gene Locus for Leber's Congenital Amaurosis and Analysis of Candidate Genes . Invest. Ophthalmol. Vis. Sci. 2002;43(13):811.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: The LCA5 locus was described as a new locus for Leber's congenital amaurosis in a single pedigree. The lod score obtained in this pedigree was 3.38, which allowing for multiple testing, remains only a tentative finding. We now report linkage of two further families from a disparate racial group to this locus, confirming the earlier report. In addition, two candidate genes, ELOVL4 and SH3BGRL2 have been excluded by sequence analysis. Methods: Linkage analysis confirmed linkage to the LCA5 locus. Candidates from among the known genes mapping to the critical interval were selected on the basis of either causing other retinal disease or pattern of expression. Results: Multipoint linkage analysis generated lod scores of 4.6 and 3.75 in the two linked families, using markers D6S391 and D6S968 at the LCA5 locus. Sequence analysis failed to show a pathogenic mutation in either the ELOVL4 gene or the SH3BGRL2 gene. Conclusion: ELOVL4 lies within the previously described LCA5 genetic interval and mutations in it cause autosomal dominant macular dystrophy. SH3BGRL2 is a gene of unknown function known to have expression in the fovea. The exclusion of these genes further underlines the genetic complexity of retinal disease in the 6q11-16 region. The finding of new families linking to the LCA5 critical interval will facilitate the identification of the causative gene for LCA5 linked Leber's congenital amaurosis.
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