The RP1 gene has been localized to chromosome 8q11.2-q12.1. This gene encodes a member of the doublecortin family. It has two doublecortin domains, which bind microtubules and regulate microtubule polymerization. The protein encoded by RP1 is a photoreceptor microtubule-associated protein and is required for regulating the stability and length of the microtubule-based axoneme of photoreceptors. The RP1 protein and the RP1L1 protein play essential and synergistic roles in affecting photosensitivity and outer segment morphogenesis of rod photoreceptors, ensuring the correct orientation and higher-order stacking of outer segment disks along the photoreceptor axoneme. Defects in this protein are the cause of retinitis pigmentosa 1 (RP1), a retinal dystrophy characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors.
Al-Rashed et al. (2012) described 20 patients from six Arab families, with autosomal recessive retinitis pigmentosa. All families were consanguineous, and five of the families were multiplex. Using linkage analysis, homozygosity mapping, and direct sequencing of the RP1 gene, four novel mutations, all recessive, were identified in the affected patients. These mutations consisted of a homozygous nonsense mutation (c.4552A>T) in one family, a homozygous single base deletion (c.3428delA) in three families, a homozygous nonsense mutation (c.33396 G>A) in a sporadic case, and a homozygous frameshift mutation (c.3677_3678dupA) in one family. All these mutations were in exon four, and resulted in a truncated RP1 protein.