Retinitis Pigmentosa 71
A number sign (#) is used with this entry because of evidence that retinitis pigmentosa-71 (RP71) is caused by homozygous or compound heterozygous mutation in the IFT172 gene (607386) on chromosome 2p23.
Mutation in the IFT172 gene also results in short-rib thoracic dysplasia-10 with or without polydactyly (SRTD10; 615630).
For a general phenotypic description and discussion of genetic heterogeneity of retinitis pigmentosa, see 268000.
Clinical FeaturesBujakowska et al. (2015) reported an unrelated woman and man with retinitis pigmentosa. The 33-year-old French woman developed night blindness in the second decade of life; examination showed RP as well as a lamellar macular hole on the left and optic nerve drusen on the right. She also had CD4 lymphopenia of unknown origin with recurrent ear, upper respiratory, and pulmonary infections. The 38-year-old Dutch man developed night blindness in the first decade of life and was diagnosed with RP at age 23 years. Additional features included preserved foveal lamination, epiretinal membrane, macular cysts, and optic nerve drusen. He had untreated scoliosis at age 11 to 12 years but reported no back problems. Neither patient was obese or exhibited polydactyly.
Clinical Variability
Bujakowska et al. (2015) reported 2 sisters, 15 and 22 years of age, with RP as well as systemic features suggesting a Bardet-Biedl-like ciliopathy (BBS; see 209900). Both were obese and had a history of delayed speech development and elevated liver transaminases. The younger sister also exhibited bilateral postaxial cutaneous polydactyly, hypercholesterolemia, and pancreatitis. Neither sib had skeletal anomalies.
Molecular GeneticsIn 2 sisters with RP and obesity, who were negative for mutation in 12 BBS-associated genes, Bujakowska et al. (2015) performed whole-exome sequencing (WES) and identified compound heterozygosity for a missense mutation (H1567Q; 607386.0013) and a splice site mutation (607386.0014) in the IFT172 gene. In a French woman with moderately severe RP, born of consanguineous parents, who was negative for mutation in known autosomal recessive RP genes, Bujakowska et al. (2015) performed homozygosity mapping followed by WES and identified homozygosity for a missense mutation in IFT172 (D1605E; 607386.0015). The mutation was located within the second largest homozygous region found, a 20.5-Mb interval on chromosome 2. In a Dutch man with RP, who was negative for mutation in 110 nonsyndromic retinal dystrophy-associated genes, Bujakowska et al. (2015) performed WES and identified compound heterozygosity for a missense mutation (L257P; 607386.0016) and a splice site mutation (607386.0017) in the IFT172 gene. The mutations segregated with disease in the respective families. Analysis of the IFT172 gene in 343 additional patients with syndromic or nonsyndromic RP did not yield any further mutations. Noting that mutations in IFT172 have also been reported to cause short-rib thoracic dysplasia (SRTD10; 615630), Bujakowska et al. (2015) proposed that the presence of modifying alleles could explain the more severe clinical manifestations of some IFT172-related phenotypes.