Much progress has been made in the past five years in the understanding of
Leber congenital amaurosis (LCA) and allied early-onset
retinal dystrophies, various forms of stationary sensory
retinal blindness, and genes that are involved in the development of the retina. Uncomplicated
Leber congenital amaurosis has been associated with mutations of six genes: GUCY2D (encoding RetGC-1) at 17p13.1, RPE65 at 1q31, CRX at 19q13.3, AIPLI at 17p13.1, CRB1 at 1q31-3, and RPGRIP at 14q11. A similar early-onset severe
retinal degeneration phenotype has been associated with mutation of TULP1 at 6p21.3. Leber appreciated that the condition he described merged with the phenotypes of early childhood-onset severe
retinal degenerations. This insight has been confirmed at the molecular level for mutations of GUCY2D, RPE65, CRX, AIPL1, and CRB1, which cause not only LCA, but also early-childhood and even adult-onset
retinal degenerations. This paper reviews the new finding of LCA from mutations of CRB1 and discusses the molecular basis of X-linked blue monochromacy, autosomal recessive congenital
achromatopsia from mutations of the genes for
ACHM2 (CNGA3) and
ACHM3 (CNGB3),
X-linked congenital stationary night blindness (CSNB) from mutations of CACNA1F (incomplete CSNB) and NYX (complete CSNB), and the
enhanced S-cone syndrome from mutation of the developmental gene, NR2E3 at 15q23, which appears to regulate the development of M- and L-cones from S-cones. These discoveries have opened new areas of cellular and developmental biology for future research into the causes of
retinal blindness.