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