A TULP1 founder mutation, p.Gln301*, underlies a recognisable congenital rod–cone dystrophy phenotype on the Arabian Peninsula. Issue 4 (23rd October 2014)

• Record Type: Journal Article
• Authors: Khan, Arif O; Bergmann, Carsten; Eisenberger, Tobias; Bolz, Hanno J
• Is Part Of: British journal of ophthalmology. Volume 99:Issue 4(2015)
• Page Start: 488
• Page End: 492
• Publication Date: 2014-10-23
• Subjects: Child health (paediatrics) -- Dystrophy -- Electrophysiology -- Retina; Ophthalmology -- Periodicals; 617.7
• DOI: 10.1136/bjophthalmol-2014-305836
• Languages: English
• ISSNs: 0007-1161

Abstract

Abstract : 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>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.