TY - JOUR
T1 - Infantile and childhood retinal blindness
T2 - A molecular perspective (The Franceschetti Lecture)
AU - Weleber, Richard G.
N1 - Funding Information:
I wish to acknowledge support from The Foundation Fighting Blindness, Research to Prevent Blindness, and many friends and colleagues who have allowed me to be part of their research. In particular, I thank Edwin Stone, Gerald Fishman, Sam Jacobson, and John Heckenlively for slides from patients with LCA and with CRB1 mutations, and N. Torben Bech-Hansen, Maria Musarella, Yozo Miyake, William Pearce, David Birch, Rocky Young, and Bill Murphey for their work on the families with complete and incomplete CSNB.
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
KW - Achromatopsia
KW - Congenital stationary night blindness
KW - Enhanced S-cone syndrome
KW - Franceschetti Lecture
KW - Leber amaurosis
KW - Molecular
KW - Retinal blindness
KW - Review
UR - http://www.scopus.com/inward/record.url?scp=0036068117&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036068117&partnerID=8YFLogxK
U2 - 10.1076/opge.23.2.71.2214
DO - 10.1076/opge.23.2.71.2214
M3 - Article
C2 - 12187427
AN - SCOPUS:0036068117
SN - 1381-6810
VL - 23
SP - 71
EP - 97
JO - Ophthalmic Genetics
JF - Ophthalmic Genetics
IS - 2
ER -