RT Journal Article A1 Vallespin, Elena A1 Cantalapiedra, Diego A1 Riveiro-Alvarez, Rosa A1 Wilke, Robert A1 Aguirre-Lamban, Jana A1 Avila-Fernandez, Almudena A1 Lopez-Martinez, Miguel Angel A1 Gimenez, Ascension A1 Jose Trujillo-Tiebas, Maria A1 Ramos, Carmen A1 Ayuso, Carmen T1 Mutation Screening of 299 Spanish Families with Retinal Dystrophies by Leber Congenital Amaurosis Genotyping Microarray JF Investigative Ophthalmology & Visual Science JO Invest. Ophthalmol. Vis. Sci. YR 2007 DO 10.1167/iovs.07-0007 VO 48 IS 12 SP 5653 OP 5661 SN 1552-5783 AB purpose. Leber Congenital Amaurosis (LCA) is one of the most severe inherited retinal dystrophies with the earliest age of onset. This study was a mutational analysis of eight genes (AIPL1, CRB1, CRX, GUCY2D, RPE65, RPGRIP1, MERTK, and LRAT) in 299 unrelated Spanish families, containing 42 patients with initial diagnosis of LCA: 107 with early-onset autosomal recessive retinitis pigmentosa (ARRP; onset <10 years of age) and 150 with non-early-onset ARRP (onset, >10 years of age). methods. Samples were studied by using a genotyping microarray (Asper Biotech, Ltd., Tartu, Estonia) followed by a family study in cases with potential digenism/triallelism. results. The frequencies of alleles carrying disease-causing mutations found in the authors’cohort using the chip were 23.8% (20/84) for LCA with 13 families carrying mutations, 6.1% (13/214) for early-onset ARRP with 12 families carrying mutations, and 4.3% (13/300) for non-early-onset ARRP with 12 families carrying mutations. CRB1 was the most frequently found mutated gene in affected Spanish families. Five families with anticipated digenism or triallelism were further studied in depth. Digenism could be discarded in all these cases; however, triallelism could not be ruled out. conclusions. CRB1 is the main gene responsible for LCA in the Spanish population. Sequence changes p.Asp1114Gly (RPGRIP1), p.Pro701Ser (GUCY2D), and p.Tyr134Phe (AIPL1) were found at similar frequencies in patients and control subjects. The authors therefore suggest that these changes be considered as polymorphism or modifier alleles, rather than as disease-causing mutations. The LCA microarray is a quick and reasonably low-cost first step in the molecular diagnosis of LCA. The diagnosis should be completed by conventional laboratory analysis as a second step. This stepwise proceeding permits detection of novel disease-causing mutations and identification of cases involving potential digenism/triallelism. Previous accurate ophthalmic diagnosis was found to be indispensable. RD 3/2/2021 UL https://doi.org/10.1167/iovs.07-0007