A TULP1 founder mutation, p.Gln301*, underlies a recognisable congenital rod-cone dystrophy phenotype on the Arabian Peninsula

Br J Ophthalmol. 2015 Apr;99(4):488-92. doi: 10.1136/bjophthalmol-2014-305836. Epub 2014 Oct 23.


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.

Keywords: Child health (paediatrics); Dystrophy; Electrophysiology; Retina.

MeSH terms

  • Alleles
  • Child
  • Child, Preschool
  • Codon, Nonsense*
  • Electroretinography
  • Eye Proteins / genetics*
  • Female
  • Founder Effect*
  • Homozygote
  • Humans
  • Male
  • Nystagmus, Pathologic / genetics
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Retinitis Pigmentosa / congenital
  • Retinitis Pigmentosa / genetics*
  • Retrospective Studies
  • Saudi Arabia
  • Tomography, Optical Coherence
  • Visual Acuity / physiology


  • Codon, Nonsense
  • Eye Proteins
  • TULP1 protein, human