ABSTRACT
Nucleotide changes within and around splice donor and acceptor sites have long been recognized as a major source of mutation in humans. It has been suggested that some mutations within coding regions may in fact be exercising their effect through splicing by disrupting Exonic Splice Enhancers. Exon splice enhancers also provided the explanation for initially puzzling correlations of genotype and phenotype in spinal muscular atrophy (SMA). Two closely related survival motor neuron genes, predicted to encode identical proteins, map to the SMA locus. Mutations in the gene encoding ABCR, a photoreceptor-specific ATP-binding cassette (ABC) transporter have been shown to be responsible, in a Mendelian pattern, for three separate clinically defined retinopathies. Mutations in rhodopsin, peripherin/RDS, cone-rod homeobox gene (CRX), aryl-hydrocarbon interacting protein-like 1 (AIPL1) and RP1 have all been found in patients with autosomal dominant retinitis pigmentosa. A molecular based rationale has been constructed for the observed digenic inheritance.
