Leber congenital amaurosis
MIM.204000
Definition: Leber congenital amaurosis (LCA), the most early-onset and severe form of all inherited retinal dystrophies, is responsible for congenital blindness.
Leber congenital amaurosis (LCA) is a congenital retinal dystrophy that was first described almost 150 years ago. LCA still remains an important cause of blindness with about 20% of children in schools for the blind being affected by it.
LCA has genetic heterogeneity and the study of this disease is elucidating the genetics and molecular interactions involved in the development of the retina.
Etiology
Twelve LCA loci have been mapped, and seven genes have been identified (2004).
LCA1 |
LCA2 |
LCA3 |
LCA4 |
LCA5 |
LCA6 |
LCA7 |
LCA8 |
LCA9 |
LCA10 |
LCA11 |
LCA12 |
Mutations in these seven genes are found in 47.5% of patients (15024725)
GUCY2D | CRB1 | RPE65 | RPGRIP1 | AIPL1 | RDH12 | TULP1 | CRX |
21.2% | 10% | 6.1% | 4.5% | 4.1% | 3.4% | 0.6% |
These genes are all expressed preferentially in the photoreceptor cells or the retinal pigment epithelium (RPE65) but they are involved in strikingly different physiologic pathways resulting in an unforeseeable physiopathologic variety.
References
Traboulsi EI, Koenekoop R, Stone EM. Lumpers or splitters? The role of molecular diagnosis in Leber congenital amaurosis. Ophthalmic Genet. 2006 Dec;27(4):113-5. PMID: 17148037
Cremers FP, van den Hurk JA, den Hollander AI. Molecular genetics of Leber congenital amaurosis. Hum Mol Genet. 2002 May 15;11(10):1169-76. PMID: 12015276