Leber congenital amaurosis is genetically heterogeneous with at least 18 known gene mutations associated with the phenotype. It is also clinically heterogeneous both within and among families and this is the major obstacle to the delineation of individual clinicogenetic entities. As more patients are genotyped, it is likely that more precise genotype-phenotype correlations will emerge. At the present time, however, it is not possible to use clinical findings alone to distinguish individual conditions.
Below are links to the genotypic and phenotypic features of the 19 known types of LCA. All cause disease in the homozygous or compound heterozygous state.
LCA type OMIM# Locus Gene Symbol
LCA 1 204000 7p13.1 GUCY2D
LCA 2 204100 1p31 RPE65**
LCA 3 604232 14q31.3 SPATA7
LCA 4 604393 17p13.1 AIPL1
LCA 5 604537 6q14.1 LCA5
LCA 6 613826 14q11 RPGRIP1
LCA 7 613829 19q13.1 CRX*
LCA 8 613835 1q31-q32 CRB1
LCA 9 608553 1p36 NMNAT1
LCA 10 611755 12q21 CEP290
LCA 11 613837 7q31.3-q332 IMPDH1
LCA 12 610612 1q32.3 RD3
LCA 13 612712 14q24.1 RDH12
LCA 14 613341 4q31 LRAT
LCA 15 613843 6p21-31 TULP1
LCA 16 614186 2q37 KCNJ13
LCA 17 615360 8q22.1 GDF6
LCA 18 608133 6p21.1 PRPH2***
It is likely that more mutant genes will be identified since these are found in only about half of patients studied in large series.
*(Heterozygous mutations in CRX may also cause a cone-rod dystrophy).
**(Mutations in RPE65 has been described as also causing retinitis pigmentosa (RP20; 613794) with choroidal involvement.)
***Mutations in PRPH2 (RDS) has also been reported to cause retinitis pigmentosa 7, choroidal dystrophy, and vitelliform macular dystrophy (179605) among others.
See also Leber Congenital Amaurosis with Early-Onset Deafness.
Mutations in the GUCY2D gene seem to be the most common being present in about 21% of LCA patients with CRB1 next at 10%.