Molecular diagnosis
To identify molecular defects in the CRB1 gene, different techniques can be used. The 'golden standard' is to determine the nucleotide sequence of all 12 exons of the gene. In case patients show typical features of RP12 or RP-Coats' complication, this is often done. However, the analysis of patients with congenital blindness is complicated by the fact that more than 10 different genes can be defective in any family with congenital blindness. On average, 10% of patients with congenital blindness show defects in the CRB1 gene, which makes sequence analysis relatively expensive. In the molecular analysis of patients with congenital blindness one aims to identify as many molecular defects as technically and financially feasible. Therefore, a new technology has emerged that enables the detection of all known congenital blindness mutations in a cost-effective and robust method. This technology is based on minute glass slides, so-called microarray DNA chips, on which each individual known defect is represented. Patients give a small blood sample and DNA is isolated from the white blood cells. A small quantity of the DNA is used to selectively increase the number of DNA fragments corresponding to the currently known 7 genes implicated in congenital blindness, among which CRB1. This DNA is then used to 'screen' the congenital blindness DNA chip and if a known mutation is present in the patient, it will be detected on the chip. In this way, molecular defects are found in approximately 35% of the patients and the costs (Euro 100,- to Euro 150,-) are quite low.
Further information for genetic testing of patients with Leber congenital amaurosis can be found at the following website: http://www.asperophthalmics.com.
Patients interested in testing for defects in the CRB1 gene or other retinal dystrophy genes should contact their local clinical geneticist. Molecular diagnosis of CRB1-associated diseases is possible in a few European institutes, e.g. the Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, in Nijmegen (www.humangenetics.nl), the Division of Development, Aging and Genetic Diseases at the Netherlands Ophthalmic Research Institute in Amsterdam, The Netherlands ( http://www.nin.knaw.nl), and in the Department of Genetics of the Necker Hospital in Paris.