Mutations in the CRB1 gene cause Leber congenital amaurosis.
OBJECTIVE
To test the hypothesis that mutations in the CRB1 gene cause Leber congenital amaurosis (LCA) and, if so, to describe the ocular phenotype of patients with LCA who harbor CRB1 sequence variations.


METHODS
One hundred ninety probands with a clinical diagnosis of LCA were selected from a cohort of 233 probands ascertained in 5 different countries. The remaining 43 probands (18%) were excluded because they harbored sequence variations in previously identified LCA genes.


METHODS
One hundred ninety unrelated individuals with LCA were screened for coding sequence mutations in the CRB1 gene with single-strand conformation polymorphism analysis followed by automated DNA sequencing.


RESULTS
Twenty-one of the 190 probands (9% of the total cohort of 233) and 2 (1.4%) of 140 controls harbored amino acid-altering sequence variations in the CRB1 gene (P =.003).


CONCLUSIONS
In our cohort of patients with LCA, coding sequence variations were observed in the CRB1 gene more frequently than in any of the other 5 known LCA-associated genes. Likely disease-causing sequence variations have now been identified in 64 (28%) of 233 subjects in this cohort.


CONCLUSIONS
Molecular diagnosis can confirm and clarify the diagnosis in an increasing fraction of patients with LCA. As genotype data accumulate, clinical phenotypes associated with specific mutations may be established. This will facilitate the counseling of patients regarding their visual prognosis and the likelihood of associated systemic anomalies.
Department of Ophthalmology and Visual Sciences, The University of Iowa College of Medicine, 200 Hawkins Dr, Iowa City, IA 52242, USA.
A J
AJ
Lotery
S G
SG
Jacobson
G A
GA
Fishman
R G
RG
Weleber
A B
AB
Fulton
P
P
Namperumalsamy
E
E
Héon
A V
AV
Levin
S
S
Grover
J R
JR
Rosenow
K K
KK
Kopp
V C
VC
Sheffield
E M
EM
Stone
D000293:Adolescent; D000328:Adult; D001766:Blindness / Q000151:congenital / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004247:DNA / Q000032:analysis; D017931:DNA Primers / Q000737:chemistry; D029721:Drosophila Proteins; D006801:Humans; D007223:Infant; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D015418:Optic Atrophies, Hereditary / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D014792:Visual Acuity
D017931:DNA Primers; D029721:Drosophila Proteins; D008565:Membrane Proteins; C064360:crb protein, Drosophila; D004247:DNA