A CRX null mutation is associated with both Leber congenital amaurosis and a normal ocular phenotype

Eduardo Silva, Jun Ming Yang, Yingying Li, Sharola Dharmaraj, Olof H. Sundin, Irene H. Maumenee

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


PURPOSE. To identify and characterize new cone rod homeobox (CRX) mutations associated with the Leber congenital amaurosis phenotype. METHODS. The human CRX gene was sequenced in 74 consecutive patients carrying the diagnosis of Leber congenital amaurosis. RESULTS. Two mutations were identified in CRX that cause frameshifts and predict severe truncations of the encoded protein. One of these, a 1-bp insertion, spares only nine N- terminal amino acids, removing the homeodomain, WSP motif, and conserved OTX domain at the C terminus. Of the CRX mutations described in the literature, this is the first that convincingly represents a null allele of the gene. Although the patient heterozygous for this null allele is affected with Leber congenital amaurosis, it was surprising that her father, who had normal vision, was heterozygous for the same mutation. CONCLUSIONS. These results strongly suggest that haploinsufficiency of CRX is not sufficient to cause a retinal disorder. Loss of function alleles of CRX appear to cause Leber congenital amaurosis through a recessive or multigenic mechanism.

Original languageEnglish (US)
Pages (from-to)2076-2079
Number of pages4
JournalInvestigative Ophthalmology and Visual Science
Issue number8
StatePublished - 2000

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience


Dive into the research topics of 'A CRX null mutation is associated with both Leber congenital amaurosis and a normal ocular phenotype'. Together they form a unique fingerprint.

Cite this