Identification of a novel rhodopsin mutation (Met-44-Thr) in a simplex case of retinitis pigmentosa

Retinitis pigmentosa (RP) is a group of genetically heterogeneous retinal degenerations that can be autosomal dominant (ADRP), autosomal recessive (ARRP), or X-linked. Approximately 30% of ADRP patients show point mutations or small deletions in the rhodopsin gene. However, over 50% of the RP patients are simplex cases (sporadic). Screening for mutations in the rhodopsin gene of 33 patients with simplex RP by denaturing gradient gel electrophoresis (DGGE) was carried out. One patient, with D-type (diffuse) RP and consanguineous parents, showed an altered electrophoretic pattern for the 5 half of exon 1. Direct sequencing revealed a new mutation ATG to ACG in codon 44; this predicts a change of Met-44-Thr in rhodopsin. The position and amino acid substitution suggest that this mutation causes the RP phenotype. Implications for genetic counselling are discussed.