1. A strategy for molecular diagnosis and search for new genes/loci in autosomal dominant retinitis pigmentosa.
- Author
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MANES, G, DHAENENS, CM, BOCQUET, B, MARQUETTE, V, BAUDOIN, C, RICHARD, AC, HEBRARD, M, MEUNIER, I, and HAMEL, C
- Subjects
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RETINITIS pigmentosa , *LOCUS (Genetics) , *GENES , *MOLECULAR diagnosis , *PILOT projects - Abstract
Purpose Autosomal dominant retinitis pigmentosa (adRP) affects approximately 1 in 12,000 individuals. To date, 24 adRP genes have been identified accounting theoretically for 44.7% of adRP families; therefore, genetic defects in many patients are yet to be identified. This study was intended to provide information on prevalence of known adRP genes in France and to localize new genes and loci. Methods The 10 most frequently mutated adRP genes (in full for RHO and RDS, in hot spots only for PRPF31, RP1, PRPF8, IMPDH1, NRL, PRPF3, NR2E3 and SNRNP200) were screened by systematic sequencing to determine the causative mutation in a cohort of 232 French families affected by adRP. We also performed a pilot experiment on 12 families by using whole exome sequencing (WES). Results The direct sequencing approach was performed on 232 proband DNAs. A causative mutation was found for 99 families (42.7 %), among which 35 out of 68 (51.5 %) were novel. Among the 133 remaining families with no mutation (57.3 %), 12 probands were subjected to WES. This allowed to identify 7 additional families with a causative mutation. Conclusion The prevalence of the genes was similar to that of the literature for most genes (e.g. RHO with 16 %), but were unexpected for others (e.g. NR2E3 with 3.9 %). The WES approach allowed us to identify a causative gene in 58.3 % of a population previously screened by direct sequencing approach. The 5 remaining families, negative with WES screen, are potentially carrying a mutation in one or more new adRP genes although an intronic mutation cannot be excluded. These 5 families are under active investigation. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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