Leber congenital amaurosis comprises a group of early-onset childhood retinal dystrophies characterized by vision loss, nystagmus, and severe retinal dysfunction. Patients usually present at birth with profound vision loss and pendular nystagmus. Electroretinogram (ERG) responses are usually nonrecordable. ... Leber congenital amaurosis comprises a group of early-onset childhood retinal dystrophies characterized by vision loss, nystagmus, and severe retinal dysfunction. Patients usually present at birth with profound vision loss and pendular nystagmus. Electroretinogram (ERG) responses are usually nonrecordable. Other clinical findings may include high hypermetropia, photodysphoria, oculodigital sign, keratoconus, cataracts, and a variable appearance to the fundus (summary by Chung and Traboulsi, 2009). For a general description and a discussion of genetic heterogeneity of LCA, see 204000.
Because the CRX gene is essential for photoreceptor maintenance and because expression of a dominant-negative CRX allele in developing retina prevented outer segment biogenesis (Furukawa et al., 1997), Freund et al. (1998) tested the hypothesis that CRX mutations ... Because the CRX gene is essential for photoreceptor maintenance and because expression of a dominant-negative CRX allele in developing retina prevented outer segment biogenesis (Furukawa et al., 1997), Freund et al. (1998) tested the hypothesis that CRX mutations are responsible for some cases of the Leber congenital amaurosis phenotype by examining the CRX gene of 74 Leber congenital amaurosis patients. Probands met the following diagnostic criteria: severe visual loss with nystagmus noted in the first few months of life, a markedly reduced or nondetectable ERG response, absence of other ocular causes for the visual disturbance, and no accompanying systemic diseases. Swaroop et al. (1999) reported a patient with LCA7 who had reduction of visual acuity to the level of counting fingers and nearly global loss of visual fields with no ability to detect light presented to her other than directly ahead. The ocular fundus showed extensive pigmentary retinopathy and ERG responses had more than 98% amplitude loss of rod and cone components. The heterozygous parents retained normal visual acuity and were relatively asymptomatic clinically, except for being photoaversive to bright lights and preferring not to drive at or after dusk. Minor changes indicative of a mild form of cone-rod dystrophy were found on color vision tests, retinoscopy, and ERG in both the mother and the father.
Using SSCP analysis and direct sequencing of PCR-amplified exons in the CRX gene in 74 LCA patients, Freund et al. (1998) identified putative disease-causing de novo deletion mutations in CRX in 2 patients with LCA7: a 2-bp deletion ... Using SSCP analysis and direct sequencing of PCR-amplified exons in the CRX gene in 74 LCA patients, Freund et al. (1998) identified putative disease-causing de novo deletion mutations in CRX in 2 patients with LCA7: a 2-bp deletion at the glu168 codon (E168del2bp; 602225.0003) and a 1-bp deletion at the gly217 codon (G217del1bp; 602225.0004). Both deletions caused frameshifts, and the predicted proteins lacked the conserved C-terminal tail. A second mutation was not found in either patient. None of the parents had the mutations, which were not found in 360 control alleles. In a patient with Leber congenital amaurosis-7, Swaroop et al. (1999) identified a homozygous missense mutation in the CRX gene (R90W; 602225.0007). Nakamura et al. (2002) reported a novel de novo deletion mutation in the CRX gene (602225.0008) in a Japanese patient with LCA7. The authors noted that this mutation was similar to the other 5 known de novo mutations in CRX because it was a heterozygous deletion of 1 or 2 basepairs in exon 3, causing a frameshift and producing a protein lacking the conserved OTX tail motif near the C terminus.