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Sara Balzano, Nicola Bedoni, Francis L Munier, Carlo Rivolta; Whole-Exome Sequencing (WES) and Homozygosity mapping reveal a new frameshift insertion in the Knobloch Syndrome gene COL18A1.. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5445.
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© ARVO (1962-2015); The Authors (2016-present)
Knobloch Syndrome (KS) is a very rare autosomal recessive disorder. It is mainly characterized by high myopia, vitreoretinal degeneration with retinal detachment, and a localized defect in the occipital region of the skull described as occipital encephalocele. The purpose of this study was to identify the causative mutations in two siblings presenting with recessive vitreoretinal degeneration but apparently no other additional signs or symptoms.
Whole-exome sequencing (WES), genomewide, SNP-based homozygosity mapping and Sanger sequencing.
Homozygosity mapping and WES revealed in the patients the presence of several homozygous genomic regions susceptible to carry the causal mutation for this pathology. One of these regions was located on chromosome 21q22.3 and included the COL18A1 gene, known to be associated with Knobloch Syndrome. Sequencing analysis confirmed the presence of a novel homozygous frameshift insertion, p.G709fs, in the two affected siblings.
The p.G709fs mutation is a newly-recognized mutation in COL18A1 that has not been described before to be present in cases with Knobloch Syndrome. Additional clinical tests are currently ongoing to determine whether this mutation cause KS or a milder phenotype characterized by vitreoretinal degeneration only.
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