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Collin, R.W.* ; van den Born, L.I.* ; Klevering, B.J.* ; de Castro-Miró, M.* ; Littink, K.W.* ; Arimadyo, K.* ; Azam, M.* ; Yazar, V.* ; Zonneveld, M.N.* ; Paun, C.C.* ; Siemiatkowska, A.M.* ; Strom, T.M. ; Hehir-Kwa, J.Y.* ; Kroes, H.Y.* ; de Faber, J.T.* ; van Schooneveld, M.J.* ; Heckenlively, J.R.* ; Hoyng, C.B.* ; den Hollander, A.I.* ; Cremers, F.P.M.*

High-resolution homozygosity mapping is a powerful tool to detect novel mutations causative of autosomal recessive RP in the Dutch population.

Invest. Ophthalmol. Vis. Sci. 52, 2227-2239 (2011)
DOI PMC
Open Access Gold as soon as Publ. Version/Full Text is submitted to ZB.
PURPOSE. To determine the genetic defects underlying autosomal recessive retinitis pigmentosa (arRP) in the Dutch population and in a subset of patients originating from other countries. The hypothesis was that, because there has been little migration over the past centuries in certain areas of The Netherlands, a significant fraction of Dutch arRP patients carry their genetic defect in the homozygous state. METHODS. High-resolution genome-wide SNP genotyping on SNP arrays and subsequent homozygosity mapping were performed in a large cohort of 186 mainly nonconsanguineous arRP families living in The Netherlands. Candidate genes residing in homozygous regions were sequenced. RESULTS. In similar to 94% of the affected individuals, large homozygous sequences were identified in their genome. In 42 probands, at least one of these homozygous regions contained one of the 26 known arRP genes. Sequence analysis of the corresponding genes in each of these patients revealed 21 mutations and two possible pathogenic changes, 14 of which were novel. All mutations were identified in only a single family, illustrating the genetic diversity within the Dutch population. CONCLUSIONS. This report demonstrates that homozygosity mapping is a powerful tool for identifying the genetic defect underlying genetically heterogeneous recessive disorders like RP, even in populations with little consanguinity.
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Publication type Article: Journal article
Document type Scientific Article
Keywords LEBER CONGENITAL AMAUROSIS; RETINALDEHYDE-BINDING PROTEIN; DOMINANT RETINITIS-PIGMENTOSA; ROD CGMP-PHOSPHODIESTERASE; NUCLEAR RECEPTOR GENE; ALPHA-SUBUNIT; PUNCTATA ALBESCENS; STARGARDT-DISEASE; RDH12 MUTATIONS; CRB1 GENE
ISSN (print) / ISBN 0146-0404
e-ISSN 1552-5783
Journal Investigative Ophthalmology & Visual Science, IOVS
Quellenangaben Volume: 52, Issue: 5, Pages: 2227-2239 Article Number: , Supplement: ,
Publisher Association for Research in Vision and Ophthalmology (ARVO)
Publishing Place Rockville
Reviewing status Peer reviewed
Institute(s) Institute of Human Genetics (IHG)