Abstract
Retinal dystrophies are a phenotypically and genetically complex group of conditions. Because of this complexity, it can be challenging in many families to determine the inheritance based on pedigree analysis alone. Clinical examinations were performed and blood samples were collected from a North American (M1186) and a consanguineous Pakistani (PKRD168) pedigree affected with two different retinal dystrophies (RD). Based on the structure of the pedigrees, inheritance patterns in the families were difficult to determine. In one family, linkage analysis was performed with markers on X-chromosome. In the second family, whole-exome sequencing (WES) was performed. Subsequent Sanger sequencing of genes of interest was performed. Linkage and haplotype analysis localized the disease interval to a 70 Mb region on the X chromosome that encompassed RP2 and RPGR in M1186 . The disease haplotype segregated with RD in all individuals except for an unaffected man (IV:3) and his affected son (V:1) in this pedigree. Subsequent analysis identified a novel RPGR mutation (p. Lys857Glu fs221X) in all affected members of M1186 except V:1. This information suggests that there is an unidentified second cause of retinitis pigmentosa (RP) within the family. A novel two-base-pair deletion (p. Tyr565Ter fsX) in CHM (choroideremia) was found to segregate with RD in PKRD168. This paper highlights the challenges of interpreting family history in families with RD and reports on the identification of novel mutations in two RD families.
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Ayyagari R, Mandal MN, Karoukis AJ et al (2005) Late-onset macular degeneration and long anterior lens zonules result from a CTRP5 gene mutation. Invest Ophthalmol Vis Sci 46:3363–3371
Berger W, Kloeckener-Gruissem B, Neidhardt J (2010) The molecular basis of human retinal and vitreoretinal diseases. Prog Retin Eye Res 29:335–375
Bowne SJ, Sullivan LS, Avery CE et al (2013) Mutations in the small nuclear riboprotein 200 kDa gene (SNRNP200) cause 1.6% of autosomal dominant retinitis pigmentosa. Mol Vis 19:2407–2417
Branham K, Othman M, Brumm M et al (2012) Mutations in RPGR and RP2 account for 15% of males with simplex retinal degenerative disease. Invest Ophthalmol Vis Sci 53:8232–8237
Churchill JD, Bowne SJ, Sullivan LS et al (2013) Mutations in the X-linked retinitis pigmentosa genes RPGR and RP2 found in 8.5% of families with a provisional diagnosis of autosomal dominant retinitis pigmentosa. Invest Ophthalmol Vis Sci 54:1411–1416
Comander J, Weigel-DiFranco C, Sandberg MA et al (2015) Visual function in carriers of X-linked retinitis pigmentosa. Ophthalmology 122:1899–1906
Duncan JL, Zhang Y, Gandhi J et al (2007) High-resolution imaging with adaptive optics in patients with inherited retinal degeneration. Invest Ophthalmol Vis Sci 48:3283–3291
Huckfeldt RM, East JS, Stone EM et al (2016) Phenotypic variation in a family with pseudodominant stargardt disease. JAMA Ophthalmol 134:580–583
Lathrop GM, Lalouel JM (1984) Easy calculations of lod scores and genetic risks on small computers. Am J Hum Genet 36:460–465
Maranhao B, Biswas P, Duncan JL et al (2014) exomeSuite: whole exome sequence variant filtering tool for rapid identification of putative disease causing SNVs/indels. Genomics 103:169–176
Sharon D, Sandberg MA, Rabe VW et al (2003) RP2 and RPGR mutations and clinical correlations in patients with X-linked retinitis pigmentosa. Am J Hum Genet 73:1131–1146
Sullivan LS, Bowne SJ, Seaman CR et al (2006) Genomic rearrangements of the PRPF31 gene account for 2.5% of autosomal dominant retinitis pigmentosa. Invest Ophthalmol Vis Sci 47:4579–4588
Vajaranant TS, Fishman GA, Szlyk JP et al (2008) Detection of mosaic retinal dysfunction in choroideremia carriers electroretinographic and psychophysical testing. Ophthalmology 115:723–729
Wu DM, Khanna H, Atmaca-Sonmez P et al (2010) Long-term follow-up of a family with dominant X-linked retinitis pigmentosa. Eye (Lond) 24:764–774
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Branham, K. et al. (2018). Identification of Novel Deletions as the Underlying Cause of Retinal Degeneration in Two Pedigrees. In: Ash, J., Anderson, R., LaVail, M., Bowes Rickman, C., Hollyfield, J., Grimm, C. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 1074. Springer, Cham. https://doi.org/10.1007/978-3-319-75402-4_28
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DOI: https://doi.org/10.1007/978-3-319-75402-4_28
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