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Z.-B. Jin, M. Mandai, Y. Hirami, T. Yokota, K. Higuchi, F. Ohtsuki, Y. Wada, M. Takahashi, N. Yoshimura, S. Kosugi; Comprehensive Screening of Causative Genes for Sporadic or Non-Mendelian Patients With Retinitis Pigmentosa. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4009. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
More than half of the retinitis pigmentosa (RP) cases are genetically simplex or multiplex. To date, 37 causative genes of RP have been identified; however, the elucidation of gene defects in simplex or multiplex RP patients/families remains problematic. The aim of our study was to identify the genetic causes of RP in patients with unknown or non-Mendelian inheritance.
Since 2003, 52 simplex (sporadic) RP patients, 151 patients from 141 multiplex (non-Mendelian inheritance) RP families, 6 sporadic patients with retinal degeneration were studied. A total of 108 exons of 30 RP-causing genes that harbored the reported mutations were screened by an efficient denaturing high-performance liquid chromatography (dHPLC)-based assay. Aberrant fragments were subsequently analyzed by automatic sequencing.
Twenty-six mutations, including 2 frameshift mutations, one single amino acid deletion, and 23 missense mutations, were identified in 28 probands (14.07%). Eighteen mutations have not been reported to date. Three pairs of combined mutations in different genes were identified in 2 sporadic cases and 1 multiplex family, indicating the possibility of novel digenic patterns.
We elucidated the mutation spectrum in Japanese RP patients and demonstrated the validity of the mutation detection system using dHPLC-sequencing for genetic diagnosis in RP patients independent of familial incidence, which may provide a model strategy for identifying genetic causes in other diseases linked to a wide range of genes.
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