MUTATION IN BRIEF HUMAN MUTATION Mutation in Brief #577 (2003) O nline © 2003 WILEY-LISS, INC. DOI: 10.1002/humu.9106 Received 14 October 2002; accepted revised manuscript 11 November 2002. Mutations in the CACNA1F and NYX Genes in British CSNBX Families Ilaria Zito 1 , Louise E. Allen 4,5 , Reshma J. Patel 1 , Alfons Meindl 6 , Keith Bradshaw 4 , John R. Yates 5 , Alan C. Bird 7 , Lynda Erskine 1,2 , Michael E. Cheetham 3 , Andrew R. Webster 1,7 , Subathra Poopalasundaram 1 , Anthony T. Moore 1,7 , Dorothy Trump 5 , and Alison J. Hardcastle 1* 1 Division of Molecular Genetics, 2 Visual Science, and 3 Pathology, Institute of Ophthalmology, UCL, London, UK; 4 Eye Department, Addenbrooke’s Hospital, Cambridge, UK; 5 Department of Medical Genetics, University of Cambridge, UK; 6 Abteilung fur padiatrische Genetik der LMU, Munchen, Germany; 7 Moorfields Eye Hospital, London, UK *Correspondence to: Dr. A.J. Hardcastle, Department of Molecular Genetics, Institute of Ophthalmology, University College London, 11-43 Bath Street, London, EC1V 9EL; E-mail: a.hardcastle@ucl.ac.uk Grant sponsor: The Wellcome Trust and The Guide Dogs for the Blind Association Communicated by Jean-Louis Mandel X-linked congenital stationary night blindness (CSNBX) is a genetically and phenotypically heterogeneous non-progressive disorder, characterised by impaired night vision but grossly normal retinal appearance. Other more variable features include reduction in visual acuity, myopia, nystagmus and strabismus. Genetic mapping studies by other groups, and our own studies of British patients, identified key recombination events indicating the presence of at least 2 disease genes on Xp11. Two causative genes ( CACNA1F and NYX) for CSNBX have now been identified through positional cloning strategies. In this report, we present the results of comprehensive mutation screening in 14 CSNBX families, three with mutations in the CACNA1F gene and 10 with mutations in the NYX gene. In one family we failed to identify the mutation after testing RP2, RPGR, NYX and CACNA1F. NYX gene mutations are a more frequent cause of CSNBX, although there is evidence for founder mutations. Our report of patient population mutation screening for both CSNBX genes, and our exclusion of RP2 and RGPR, indicates that mutations in CACNA1F and NYX are likely to account for all CSNBX. © 2003 Wiley-Liss, Inc. KEY WORDS: X-linked congenital stationary night blindness, NYX, CACNA1F INTRODUCTION Congenital stationary night blindness (CSNB) denotes a series of non-progressive retinal disorders inherited as autosomal dominant (adCSNB), autosomal recessive (arCSNB), or X-linked (CSNBX) diseases. Genetic studies of X-linked congenital stationary night blindness families by several groups identified close linkage to markers on proximal Xp (MIM#s 300071 and 310500), and genetic heterogeneity for CSNBX was established (Bech-Hansen et al., 1993; Bergen et al ., 1995). We identified a key family of British origin, which defined a genetic location for CSNBX (named CSNB1 or CSNB4) between the retinitis pigmentosa loci RP2 and RP3, therefore excluding allelic heterogeneity with X-linked retinitis pigmentosa in this family (Hardcastle et al ., 1997), and defining the locus for the second CSNBX gene on Xp11. CSNBX shows clinical heterogeneity but the characteristic finding in affected individuals is the “negative wave” electroretinogram (ERG) described by Schubert and Bornschein (Schubert and Bornschein 1952;