科研之友
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摘要
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 (TULPI, c.901C>T (p.GIn301*)) 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.GIn301* mutation in TULPI 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.GIn301* mutation (detected after next-generation sequencing) and 12 ethnically matched controls. TULPI haplotypes were constructed by analysis of TULPI 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.GIn301* and was not present in controls. Conclusions The TULPI allele p.GIn301* represents a founder mutation on the Arabian Peninsula and is associated with a recognisable congenital recessive rod-cone dystrophy phenotype in the homozygous state.
- 出版日期2015-4
