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L.S. Sullivan, S.J. Bowne, S.P. Shankar, S.H. Blanton, J.R. Heckenlively, D.G. Birch, D.H. Wheaton, M.Z. Pelias, S.P. Daiger; Linkage Mapping in Families With Autosomal Dominant Retinitis Pigmentosa (adRP) . Invest. Ophthalmol. Vis. Sci. 2005;46(13):2293.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Genes known to cause adRP account for no more than 50% of tested families. The purpose of this project was to identify new adRP genes by a systematic approach to mutation screening and linkage mapping. Methods: DNAs of probands from over 200 adRP families were tested for mutations in known genes by sequencing. Families of probands without mutations were then tested for linkage to a panel of STR markers flanking and within known adRP genes and X–linked RP genes. Subsequently, DNAs from three large adRP families (UTAD388, RFS132, UTAD003) without mutations in or linkage to known genes were submitted for genome–wide linkage testing. Linkage markers were tested at the UCLA Sequencing and Genotyping Center using the ABI High Density 5cM STR marker set. DNAs from a total of 13, 8 and 9 affected family members from the three families, respectively, were tested. Data analysis included multipoint linkage testing using the LINKAGE analysis package, setting penetrance to 90% and disease allele frequency to 0.001. Results: Of the three families, family UTAD388 shows a maximum multipoint LOD score of 3.4 to chromosome 12 markers, family RFS132 shows a maximum LOD score of 1.7 to the same region on chromosome 12, and family UTAD003 shows no significant LOD scores in the first 50% of markers tested. UTAD388 is a Taiwanese family with late onset and slow progression of disease; RFS132 is an African American family also with late onset and slow progression; and UTAD003 is an Acadian American family with more severe disease phenotype. Conclusions: These data confirm that additional genes are involved in adRP. The region of chromosome 12 implicated in this study is not currently known to harbor genes causing dominant retinopathies but several apparent candidates are included. A systematic approach to family ascertainment, mutation screening and linkage testing is an effective way to identify new adRP genes.
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