Mutation analysis of 3 genes in patients with Leber congenital amaurosis.
OBJECTIVE
To assess the frequency of mutations in the CRX, GUCY2D, and RPE65 genes in patients with Leber congenital amaurosis (LCA).


METHODS
One hundred seventy-six probands with a clinical diagnosis of LCA were from 9 countries, with the largest subgroup being 39 probands from India.


METHODS
Samples were screened with single-strand conformation polymorphism analysis followed by DNA sequencing of 3 genes (CRX, GUCY2D, and RPE65) known to be associated with LCA.


RESULTS
Of the 176 probands, 28 (15.9%) harbored possible disease-causing mutations. The relative contribution of each gene to the total number of mutations was as follows: CRX, 2.8%; GUCY2D, 6.3%; and RPE65, 6.8%. No patients who harbored mutations in these genes had associated systemic abnormalities. Molecular diagnosis allowed definitive genetic counseling in a family affected with Best disease and LCA.


CONCLUSIONS
Molecular diagnosis may be of benefit to patients affected with LCA. The relative paucity of mutations found in this study suggests that more LCA-associated genes remain to be discovered.


CONCLUSIONS
Molecular diagnosis can confirm and clarify the diagnosis of LCA. As genotype data accumulate, clinical phenotypes associated with specific mutations will be established. This will facilitate the counseling of patients on their visual prognosis and the likelihood of associated systemic anomalies.
Lotery
A J
AJ
Department of Ophthalmology and Visual Sciences, University of Iowa Hospitals and Clinics, Iowa City, USA.
Namperumalsamy
P
P
Jacobson
S G
SG
Weleber
R G
RG
Fishman
G A
GA
Musarella
M A
MA
Hoyt
C S
CS
Héon
E
E
Levin
A
A
Jan
J
J
Lam
B
B
Carr
R E
RE
Franklin
A
A
Radha
S
S
Andorf
J L
JL
Sheffield
V C
VC
Stone
E M
EM
D000293:Adolescent; D000328:Adult; D001766:Blindness / Q000151:congenital / Q000175:diagnosis / Q000235:genetics*; D002352:Carrier Proteins; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000032:analysis*; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005817:Genetic Counseling; D006162:Guanylate Cyclase / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D015418:Optic Atrophies, Hereditary / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D011506:Proteins / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics*; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase
D002352:Carrier Proteins; D004247:DNA; D005136:Eye Proteins; D006162:Guanylate Cyclase; D018398:Homeodomain Proteins; D011506:Proteins; D015534:Trans-Activators; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase; C109288:cone rod homeobox protein