PT - JOURNAL ARTICLE AU - Arif O Khan AU - Carsten Bergmann AU - Tobias Eisenberger AU - Hanno J Bolz TI - A <em>TULP1</em> founder mutation, p.Gln301*, underlies a recognisable congenital rod–cone dystrophy phenotype on the Arabian Peninsula AID - 10.1136/bjophthalmol-2014-305836 DP - 2015 Apr 01 TA - British Journal of Ophthalmology PG - 488--492 VI - 99 IP - 4 4099 - http://bjo.bmj.com/content/99/4/488.short 4100 - http://bjo.bmj.com/content/99/4/488.full SO - Br J Ophthalmol2015 Apr 01; 99 AB - Background In Arabian children referred with retinal dystrophy, we have observed that a specific biallelic nonsense mutation in the gene encoding tubby-like protein 1 (TULP1, c.901C&gt;T (p.Gln301*)) is recurrent. This makes the mutation and its associated childhood retinopathy particularly interesting for genetic diagnostic and, potentially, gene therapy approaches. We characterise the ophthalmic phenotype associated with recessive p.Gln301* mutation in TULP1 and assess the mutation for single founder effect. Methods Retrospective consecutive case series (2011–2014) of 10 Arabian children (8 families) homozygous for the p.Gln301* mutation (detected after next-generation sequencing) and 12 ethnically matched controls. TULP1 haplotypes were constructed by analysis of TULP1 intragenic single nucleotide polymorphisms from next-generation sequencing data and genotyping of gene-flanking polymorphic microsatellite markers. Results All 10 children (2–8 years old; mean 5.2, median 6) had nystagmus since soon after birth, a grossly normal posterior pole other than arteriolar attenuation, peripheral mottling with apparent evolution to bone spicules, and hyperopia. Rod function was non-recordable while cone function was present (albeit depressed and delayed); however, repeat electroretinogram years later in two children revealed loss of recordable cone function. Autofluorescence showed a hyper-fluorescent ring around the fovea while central optical coherence tomography was within normal limits. A specific haplotype was associated with p.Gln301* and was not present in controls. Conclusions The TULP1 allele p.Gln301* represents a founder mutation on the Arabian Peninsula and is associated with a recognisable congenital recessive rod–cone dystrophy phenotype in the homozygous state.