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. 2009 Mar;50(3):1336-43.
doi: 10.1167/iovs.08-2589. Epub 2008 Oct 20.

Mutation survey of known LCA genes and loci in the Saudi Arabian population

Yumei Li  1 , Hui Wang, Jianlan Peng, Richard A Gibbs, Richard Alan Lewis, James R Lupski, Graeme Mardon, Rui Chen
Affiliations

Mutation survey of known LCA genes and loci in the Saudi Arabian population

Yumei Li et al. Invest Ophthalmol Vis Sci. 2009 Mar.

Abstract

Purpose: The purpose of this study was to perform a comprehensive survey of all known Leber congenital amaurosis (LCA) genes and loci in a collection of 37 consanguineous LCA families from Saudi Arabia.

Methods: Direct PCR and sequencing were used to screen 13 known LCA genes (GUCY2D, CRX, RPE65, TULP1, AIPL1, CRB1, RPGRIP1, LRAT, RDH12, IMPDH1, CEP290, RD3, LCA5). In addition, families without mutations identified were further screened with STR markers around these 13 known LCA genes and two loci.

Results: Disease-causing mutations were identified in nine of the 37 families: five in TULP1, two in CRB1, one in RPE65, and one in GUCY2D. Mutations in known genes only accounted for 24% of the Saudi families--much less than what has been observed in the European population (65%). Phenotype-genotype analysis was carried out to investigate the LCA disease penetrance for all families whose mutations identified. All identified mutations were found to segregate perfectly with the disease phenotype. On the other hand, severity of the disease varies for different patients carrying the same mutation and even within the same family. Furthermore, based on homozygosity mapping with both STR and SNP markers, one family is likely to map to the LCA3 locus.

Conclusions: These results underscore the importance of studying LCA disease families from different ethnic backgrounds to identify additional novel LCA disease genes. Furthermore, perfect segregation between mutation and disease indicates that LCA is fully penetrant. However, phenotypic variations among patients carrying the same mutation suggest that at least some of the variations in the clinical phenotype is due to modification from the genetic background, environment, or other factors.

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Figures

Figure 1
Figure 1
Pedigrees of nine families with mutations in known LCA genes. Pedigrees are drawn using the HaploPainter program. Solid shapes represent affected members. DNA from patients whose identifiers start with n is not available.
Figure 2
Figure 2
Pedigree and haplotype of KKESH-060 that mapped to the LCA3 locus.
See this image and copyright information in PMC

References

    1. Leber T. Ueber retinitis pigmentosa und angeborene Amaurose. Albrecht von Graefes Arch Ophthal. 1869;15(3):1–25.
    1. Perrault I, Rozet JM, Calvas P, et al. Retinal-specific guanylate cyclase gene mutations in Leber's congenital amaurosis. Nat Genet. 1996;14(4):461–464. - PubMed
    1. Koenekoop RK. An overview of Leber congenital amaurosis: a model to understand human retinal development. Surv Ophthalmol. 2004;49(4):379–398. - PubMed
    1. Lewis RA. Retinal Dystrophies and Degenerations. Raven Press; New York: 1988. Juvenile Hereditary Macular Dystrophies; pp. 115–134.
    1. Dharmaraj SR, Silva ER, Pina AL, et al. Mutational analysis and clinical correlation in Leber congenital amaurosis. Ophthalmic Genet. 2000;21(3):135–150. - PubMed

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