Abstract
Mutations in retinitis pigmentosa GTPase regulator (RPGR) account for over 70% of X-linked retinitis pigmentosa (XlRP), characterized by retinal degeneration and eventual blindness. RPGR mutations demonstrate extreme phenotypic heterogeneity, even within the same family, suggesting a role for genetic modifiers in disease expression. This study aimed to categorize the clinical diversity in a cohort of 98 affected males from 56 families with RPGR mutations, and to test candidate modifier genes for association with disease severity. Ninety-eight affected males from 56 families were enrolled. Patients were categorized as mild, moderate, or severe according to specific clinical criteria. Patient DNA was genotyped for common coding SNPs in four candidate modifier genes known to interact with RPGR: RPGRIP1, RPGRIP1L, CEP290, and NPHP5. Family-based association testing was performed using PLINK (pngu.mgh.harvard.edu/purcell/plink/). A wide range of severity was observed between and within families. Two SNPs showed association with severe disease: the minor allele (N) of I393N in IQCB1 (p = 0.044) and the common allele (R) of R744Q in RPGRIP1L (p = 0.049).
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Acknowledgments
We thank James Hixson for the monsomic cell line DNA, Hemaxi Patel for assistance in visual function testing, and Martin Klein for assistance in creating Fig. 41.1. This work was funded by the Foundation Fighting Blindness and NEI/NIH grant EY007142 to SPD.
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Fahim, A.T. et al. (2012). Polymorphic Variation of RPGRIP1L and IQCB1 as Modifiers of X-Linked Retinitis Pigmentosa Caused by Mutations in RPGR. In: LaVail, M., Ash, J., Anderson, R., Hollyfield, J., Grimm, C. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 723. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-0631-0_41
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