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 reti nal degenerations that can be autosomal dominant (ADRP), autosomal rec essive (ARRP), or X-linked. Approximately 30% of ADRP patients show po int mutations or small deletions in the rhodopsin gene. However, over 50% of the RP patients are simplex cases (sporadic). Screening for mut ations in the rhodopsin gene of 33 patients with simplex RP by denatur ing 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 g enetic counselling are discussed.