These data show that ablation of Rom1 results in the conversion of an MD/PD phenotype characterized by cone functional defects and the formation of abnormal Prph2/Rom1 complexes to an RP phenotype characterized by rod-dominant functional defects and reductions in total Prph2 protein.
Moreover, heterozygous mutations in ROM1 on 11q13, in combination with heterozygous mutations in RDS on 6p21.1-cen, cause digenic RP (the two-locus mechanism).
Individuals who coinherit a L185P peripherin-2 mutation and a null or G113Erom-1 mutation are afflicted with retinitis pigmentosa, whereas individuals who inherit only one defective gene are normal.
Although most disease phenotypes appear to result from defects at single genetic loci (monogenic), at least one instance of RP appears to require a coinheritance of defects in the unlinked peripherin/rds and rom-1 alleles (digenic), which encode the polypeptide subunits of an oligomeric transmembrane protein complex present at photoreceptor outer segment disc rims.
Four ROM1 alleles were designated as potentially pathogenic because they were found only in RP patients but not in 50-100 controls nor in 249 other RP probands.