• S P Brooks, N D Ebenezer, S Poopalasundaram, O J Lehmann, A T Moore, and A J Hardcastle.
• Division of Molecular Genetics, Institute of Ophthalmology, 11-43 Bath Street, London, EC1V 9EL, UK.
• J. Med. Genet. 2004 Oct 1; 41 (10): 768-71.

BackgroundThe disease intervals for Nance-Horan syndrome (NHS [MIM 302350]) and X linked congenital cataract (CXN) overlap on Xp22.ObjectiveTo identify the gene or genes responsible for these diseases.MethodsFamilies with NHS were ascertained. The refined locus for CXN was used to focus the search for candidate genes, which were screened by polymerase chain reaction and direct sequencing of potential exons and intron-exon splice sites. Genomic structures and homologies were determined using bioinformatics. Expression studies were undertaken using specific exonic primers to amplify human fetal cDNA and mouse RNA.ResultsA novel gene NHS, with no known function, was identified as causative for NHS. Protein truncating mutations were detected in all three NHS pedigrees, but no mutation was identified in a CXN family, raising the possibility that NHS and CXN may not be allelic. The NHS gene forms a new gene family with a closely related novel gene NHS-Like1 (NHSL1). NHS and NHSL1 lie in paralogous duplicated chromosomal intervals on Xp22 and 6q24, and NHSL1 is more broadly expressed than NHS in human fetal tissues.ConclusionsThis study reports the independent identification of the gene causative for Nance-Horan syndrome and extends the number of mutations identified.

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