Retinitis Pigmentosa 14
A number sign (#) is used with this entry because of evidence that retinitis pigmentosa-14 (RP14) is caused by homozygous or compound heterozygous mutation in the TULP1 gene (602280) on chromosome 6p21.
Mutation in TULP1 can also cause a form of Leber congenital amaurosis (LCA15; 613843) as well as juvenile retinitis pigmentosa (see 613843).
For a phenotypic description and a discussion of genetic heterogeneity of retinitis pigmentosa and juvenile RP, see 268000.
MappingIn a large pedigree from the Dominican Republic showing segregation for autosomal recessive retinitis pigmentosa, Knowles et al. (1994) demonstrated linkage to microsatellite markers on 6p. The results of 2-point and multipoint analyses suggested that the most likely location of the disease gene is near D6S291, which is located approximately 20 cM telomeric of the photoreceptor peripherin locus (PRPH2; 179605).
Molecular GeneticsMutations in the PRPH2 gene cause autosomal dominant retinitis pigmentosa as well as other forms of macular dystrophy and retinopathy. Knowles et al. (1994) used a mononucleotide repeat polymorphism in the peripherin gene to show that PRPH2 was not the site of the mutation in the Dominican kindred. In 2 extended Dominican kindreds, Banerjee et al. (1998) demonstrated a splice site mutation in the TULP1 gene in homozygous state (602280.0005) in affected individuals and heterozygous state in obligate carriers.
Among 162 patients with nonsyndromic recessive retinitis pigmentosa and 374 simplex cases of RP, Hagstrom et al. (1998) found 2 who were compound heterozygotes for mutations in the TULP1 gene (e.g., 602280.0001, 602280.0003). Three of the mutations were missense changes affecting the conserved C-terminal region; the fourth mutation (602280.0004) affected a splice donor site upstream of this region.
Kondo et al. (2004) found a phe382-to-ser mutation in the TULP1 gene (602280.0006) in a Japanese patient with retinitis pigmentosa and her brother. Although the clinical features of these sibs matched well with previously reported features, the patients lacked severe central vision dysfunction and nystagmus, which had been regarded as characteristic findings at all stages of the disease (Lewis et al., 1999), suggesting that this mutation results in a relatively mild reduction of protein function.
Den Hollander et al. (2007) described 5 members of a Surinamese family with RP14 who were compound heterozygous for mutations in the TULP1 gene (602280.0007-602280.0008). All 5 had a severe early-onset retinal dystrophy with a history of nystagmus, low visual acuity, and night blindness since infancy. Scotopic and photopic responses were nonrecordable on electroretinography.
Kannabiran et al. (2012) studied 26 families from southern India segregating autosomal recessive RP, 16 of which mapped to known autosomal recessive RP or retinal dystrophy genes. Screening of known RP genes revealed mutations in 3 families, including a homozygous missense mutation in the TULP1 gene in 3 sibs.