Novel compound heterozygous TULP1 mutations in a family with severe early-onset retinitis pigmentosa

Objective: To describe the clinical characteristics and determine the genetic defect in a Surinamese family with autosomal recessive retinitis pigmentosa. Methods: Family members underwent blood sampling and ophthalmologic examinations. After exclusion of all known mutations in all genes involved in autosomal recessive retinitis pigmentosa, a genome-wide linkage scan was performed using 11 555 single-nucleotide polymorphisms spread throughout the genome. Mutation analysis of the TULP1 gene was performed by direct sequencing. Results: All affected family members had a severe retinal dystrophy with a history of nystagmus, low visual acuity, and nyctalopia since infancy. The scotopic and photopic responses were nonrecordable on electroretinography. A genome-wide scan suggested linkage to the chromosomal region containing the TULP1 gene. Mutation analysis of TULP1 identified novel compound heterozygous mutations ( p. Arg482Trp and p. Leu504fsX140) in all affected family members. Conclusions: 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. Clinical Relevance: Clinical and molecular genetic characterization of autosomal recessive retinitis pigmentosa may help to provide a more accurate prognosis in individual patients. This study confirms that TULP1 mutations cause a severe early-onset form of autosomal recessive retinitis pigmentosa.