Human pathology

Home page > E. Pathology by systems > Nervous system > Sensorial system > Eyes > Leber congenital amaurosis

Leber congenital amaurosis

MIM.204000

LCA, congenital retinal blindness

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