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A TULP1 founder mutation, p.Gln301*, underlies a recognisable congenital rod–cone dystrophy phenotype on the Arabian Peninsula
  1. Arif O Khan1,
  2. Carsten Bergmann2,
  3. Tobias Eisenberger2,
  4. Hanno J Bolz2,3,4
  1. 1Division of Pediatric Ophthalmology, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia
  2. 2Bioscientia Center for Human Genetics, Ingelheim, Germany
  3. 3Renal Division, Department of Medicine, University Medical Center Freiburg, Freiburg, Germany
  4. 4Institute of Human Genetics, University Hospital of Cologne, Cologne, Germany
  1. Correspondence to Dr Arif O Khan, Division of Pediatric Ophthalmology, King Khaled Eye Specialist Hospital, Riyadh 11462, Saudi Arabia; arif.khan{at}


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.

  • Child health (paediatrics)
  • Dystrophy
  • Electrophysiology
  • Retina

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