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A. J. Hardcastle, M. Coccia, S. P. Brooks, K. Christodoulou, I. Russell-Eggitt; Novel Mutations Causing Nance-Horan Syndrome and Phenotypic Variability. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4123.
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To identify the underlying genetic basis for Nance-Horan Syndrome in a series of patients and evaluate the phenotypic variability.
Ten families were diagnosed with Nance-Horan Syndrome (NHS). Family members were examined by clinical geneticists and ophthalmologists. DNA was extracted for mutation screening of the Nance-Horan Syndrome gene (NHS). Exons 1-8 of the NHS gene, including exons 1a, 1c and 3b were amplified and sequenced. For each mutation detected segregation was tested, where possible, and control chromosomes screened.
All ten affected families had typical features of NHS including congenital cataract, dental anomalies and dysmorphism. Disease in six families was attributed to a protein truncation mutation in the NHS gene in exons 1a, 2, 3, 6 or 8. No mutations were identified in the remaining four families. Of the six families with NHS gene mutations, two had developmental delay and other phenotypes in this patient group included delayed motor development and bilateral hearing loss.
We have identified novel mutations in the NHS gene causing Nance-Horan Syndrome. Variability of phenotype was noted, with symptoms not previously associated with NHS. Currently, it is not clear what leads to variability of phenotype but age of diagnosis, genetic and environmental factors may all play a role. This is the first report of a mutation in either exon 2 or exon 8 of the NHS gene. Four families with clinical features of NHS lack a molecular diagnosis, which suggests that NHS may be genetically heterogeneous, or that mutations lie outside known coding exons.
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