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

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

Author information

1
Division of Pediatric Ophthalmology, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.
2
Bioscientia Center for Human Genetics, Ingelheim, Germany.
3
Bioscientia Center for Human Genetics, Ingelheim, Germany Renal Division, Department of Medicine, University Medical Center Freiburg, Freiburg, Germany Institute of Human Genetics, University Hospital of Cologne, Cologne, Germany.

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.

KEYWORDS:

Child health (paediatrics); Dystrophy; Electrophysiology; Retina

[Indexed for MEDLINE]

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