Pathogenic mutations in TULP1 are responsible for the RP phenotype in seven familial cases with a common ancestral mutation responsible for the disease phenotype in four of the seven families.
Analysis of variants in the exome sequence data revealed a novel homozygous nonsense mutation (c.1081C > T, p.Arg361*) in TULP1, a gene with roles in photoreceptor function where mutations were previously shown to cause LCA and retinitis pigmentosa.
After exclusion of 28 subjects, 169 patients with the diagnosis of LCA and 27 patients with early childhood-onset RP were included in the study because the underlying mutations in AIPL1, GUCY2D, RDH12, RPE65, CRX, CRB1, RPGRIP1, CEP290, LCA5, and TULP1 genes could be identified in this cohort of patients.
The affected members of the Surinamese family have a severe early-onset form of autosomal recessive retinitis pigmentosa, which is caused by compound heterozygous mutations in the TULP1 gene.
Similarly to tubby mice, Tulp1 (-/-)mice exhibit an early-onset retinal degeneration with a progressive, rapid loss of photoreceptors, further supporting the notion that previously identified mutations within the human TULP1 gene are indeed causative of retinitis pigmentosa.
Our data suggest that mutations in TULP1 are a rare cause of recessive RP and indicate that TULP1 has an essential role in the physiology of photoreceptors.