Leber's congenital amaurosis (LCA) is a group of rare inherited retinal dystrophies characterized by vision loss, often from birth. LCA is the most severe form of all inherited retinal dystrophies, accounting for at least 5% of these, and is one of the main causes of blindness in children. The estimated birth prevalence of LCA is two to three per 100,000 births. There are at least 13 types of Leber congenital amaurosis. These types are distinguished by their genetic cause, patterns of vision loss, and related eye abnormalities.
Clinical diagnosis is based on clinical history of failure to develop reactions to visual stimuli, roving eye movements or nystagmus, sluggish pupillary responses and a normal, or less frequently an abnormal fundus on dilated fundoscopy. To date, no definitive treatment or cure for LCA exists.
Leber's congenital amaurosis is generally inherited in an autosomal recessive pattern, although some autosomal dominant families have been reported. At least 20 different genes involved in LCA have been identified. All these genes are necessary for normal vision, and play a variety of roles in the development and function of the retina. Mutations in the CRB1 gene are associated with the most severe phenotype of LCA disease; LCA type 8. The CRB1 gene is expressed in the inner nuclear layer, the iris and specific structures of the brain. It is essential for the normal development of photoreceptors.
Gerber et al. (2002) identified a large consanguineous Arab family of Palestinian origin with multiple members affected with LCA. A genome wide screen for homozygosity showed no linkage to any of the then known six LCA genes, but showed linkage to a region on chromosome 1q, which carried the CRB1 gene. A mutation was identified in this gene in the affected members.
Li et al. (2009) studied 37 Saudi multigenerational consanguineous families with Leber congenital amaurosis. Of the 417 individuals from these families, 117 were affected. All affected patients had early loss of vision, with variations in the clinical phenotypes. One of the families was found to carry mutations in CRB1, indicating the presence of LCA8 in the patients from this families. There were two affected siblings in this family, born to healthy consanguineous parents. The patients showed bilateral enophthalmos, irregular nystagmus, vascular attenuation, and optic atrophy. All affected members were found to be homozygous for the mutations.
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