ORPHA: 65; DO: 0110216;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 7q32.1 | Leber congenital amaurosis 11 | 613837 | Autosomal dominant | 3 | IMPDH1 | 146690 |
A number sign (#) is used with this entry because Leber congenital amaurosis-11 (LCA11) is caused by heterozygous mutation in the IMPDH1 gene (146690) on chromosome 7q32.
Heterozygous mutation in the IMPDH1 gene can also cause retinitis pigmentosa-10 (RP10; 180105).
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.
Bowne et al. (2006) described 2 unrelated patients with Leber congenital amaurosis. The affected child in 1 family was first seen at 8 months of age when he was diagnosed with LCA and developmental delay with severe hypotonia. He had roving nystagmus with no fixation to light. Macular reflex was present in both eyes with the retina showing diffuse RPE mottling. No pigmentary deposits were present. The affected child in the other family was seen after referral at age 33 months. The parents had noted that the child could not see things in her peripheral vision and could not find her food in dimly lighted conditions. Refractive error was OD +3.50+1.50 x 85, and OS +3.50+1.50 x 95. By Allen cards, her vision was 20/40.
In 2 unrelated patients with Leber congenital amaurosis-11, Bowne et al. (2006) identified heterozygous missense mutations in the IMPDH1 gene (146690.0004 and 146690.0005).
Bowne, S. J., Sullivan, L. S., Mortimer, S. E., Hedstrom, L., Zhu, J., Spellicy, C. J., Gire, A. I., Hughbanks-Wheaton, D., Birch, D. G., Lewis, R. A., Heckenlively, J. R., Daiger, S. P. Spectrum and frequency of mutations in IMPDH1 associated with autosomal dominant retinitis pigmentosa and Leber congenital amaurosis. Invest. Ophthal. Vis. Sci. 47: 34-42, 2006. [PubMed: 16384941] [Full Text: https://doi.org/10.1167/iovs.05-0868]
Chung, D. C., Traboulsi, E. I. Leber congenital amaurosis: clinical correlations with genotypes, gene therapy trials update, and future directions. J. AAPOS 13: 587-592, 2009. [PubMed: 20006823] [Full Text: https://doi.org/10.1016/j.jaapos.2009.10.004]