33
Views
2
CrossRef citations to date
0
Altmetric
Review

Genetics of Leber congenital amaurosis: an update

, &
Pages 141-151 | Published online: 09 Jan 2014

References

  • Ahmed E, Loewenstein J. Leber congenital amaurosis: disease, genetics and therapy. Semin. Ophthalmol.23(1), 39–43 (2008).
  • Den Hollander AI, Roepman R, Koenekoop RK, Cremers FP. Leber congenital amaurosis: genes, proteins and disease mechanisms. Prog. Retin. Eye Res.27(4), 391–419 (2008).
  • Koenekoop RK. An overview of Leber congenital amaurosis: a model to understand human retinal development. Surv. Ophthalmol.49(4), 379–398 (2004).
  • Stone EM. Leber congenital amaurosis – a model for efficient genetic testing of heterogeneous disorders: LXIV Edward Jackson Memorial Lecture. Am. J. Ophthalmol.144(6), 791–811 (2007).
  • Bowne SJ, Sullivan LS, Mortimer SE et al. Spectrum and frequency of mutations in IMPDH1 associated with autosomal dominant retinitis pigmentosa and Leber congenital amaurosis. Invest. Ophthalmol. Vis. Sci.47(1), 34–42 (2006).
  • Sohocki MM, Sullivan LS, Mintz-Hittner HA et al. A range of clinical phenotypes associated with mutations in CRX, a photoreceptor transcription-factor gene. Am. J. Hum. Genet.63(5), 1307–1315 (1998).
  • Camuzat A, Dollfus H, Rozet JM et al. A gene for Leber’s congenital amaurosis maps to chromosome 17p. Hum. Mol. Genet.4(8), 1447–1452 (1995).
  • Perrault I, Rozet JM, Calvas P et al. Retinal-specific guanylate cyclase gene mutations in Leber’s congenital amaurosis. Nat. Genet.14(4), 461–464 (1996).
  • Bainbridge JW, Smith AJ, Barker SS et al. Effect of gene therapy on visual function in Leber’s congenital amaurosis. N. Engl. J. Med.358(21), 2231–2239 (2008).
  • Maguire AM, Simonelli F, Pierce EA et al. Safety and efficacy of gene transfer for Leber’s congenital amaurosis. N. Engl. J. Med.358(21), 2240–2248 (2008).
  • Cideciyan AV, Aleman TS, Boye SL et al. Human gene therapy for RPE65 isomerase deficiency activates the retinoid cycle of vision but with slow rod kinetics. Proc. Natl Acad. Sci. USA105(39), 15112–15117 (2008).
  • Friedman JS, Chang B, Kannabiran C et al. Premature truncation of a novel protein, RD3, exhibiting subnuclear localization is associated with retinal degeneration. Am. J. Hum. Genet.79(6), 1059–1070 (2006).
  • Sweeney MO, Mcgee TL, Berson EL, Dryja TP. Low prevalence of lecithin retinol acyltransferase mutations in patients with Leber congenital amaurosis and autosomal recessive retinitis pigmentosa. Mol. Vis.13, 588–593 (2007).
  • Gerber S, Hanein S, Perrault I et al. Mutations in LCA5 are an uncommon cause of Leber congenital amaurosis (LCA) type II. Hum. Mutat.28(12), 1245 (2007).
  • Den Hollander AI, Koenekoop RK, Mohamed MD et al. Mutations in LCA5, encoding the ciliary protein Lebercilin, cause Leber congenital amaurosis. Nat. Genet.39(7), 889–895 (2007).
  • Li L, Xiao X, Li S et al. Detection of variants in 15 genes in 87 unrelated Chinese patients with Leber congenital amaurosis. PLoS One6(5), e19458 (2011).
  • Dharmaraj S, Leroy BP, Sohocki MM et al. The phenotype of Leber congenital amaurosis in patients with AIPL1 mutations. Arch. Ophthalmol.122(7), 1029–1037 (2004).
  • Hanein S, Perrault I, Gerber S et al. Leber congenital amaurosis: comprehensive survey of the genetic heterogeneity, refinement of the clinical definition, and genotype–phenotype correlations as a strategy for molecular diagnosis. Hum. Mutat.23(4), 306–317 (2004).
  • Perrault I, Hanein S, Gerber S et al. Retinal dehydrogenase 12 (RDH12) mutations in Leber congenital amaurosis. Am. J. Hum. Genet.75(4), 639–646 (2004).
  • Yzer S, Leroy BP, De Baere E et al. Microarray-based mutation detection and phenotypic characterization of patients with Leber congenital amaurosis. Invest. Ophthalmol. Vis. Sci.47(3), 1167–1176 (2006).
  • Zernant J, Kulm M, Dharmaraj S et al. Genotyping microarray (disease chip) for Leber congenital amaurosis: detection of modifier alleles. Invest. Ophthalmol. Vis. Sci.46(9), 3052–3059 (2005).
  • Vallespin E, Cantalapiedra D, Riveiro-Alvarez R et al. Mutation screening of 299 Spanish families with retinal dystrophies by Leber congenital amaurosis genotyping microarray. Invest. Ophthalmol. Vis. Sci.48(12), 5653–5661 (2007).
  • Coppieters F, Casteels I, Meire F et al. Genetic screening of LCA in Belgium: predominance of CEP290 and identification of potential modifier alleles in AHI1 of CEP290-related phenotypes. Hum. Mutat.31(10), E1709–E1766 (2010).
  • Wiszniewski W, Lewis RA, Stockton DW et al. Potential involvement of more than one locus in trait manifestation for individuals with Leber congenital amaurosis. Hum. Genet.129(3), 319–327 (2011).
  • Perrault I, Delphin N, Hanein S et al. Spectrum of NPHP6/CEP290 mutations in Leber congenital amaurosis and delineation of the associated phenotype. Hum. Mutat.28(4), 416 (2007).
  • Den Hollander AI, Koenekoop RK, Yzer S et al. Mutations in the CEP290 (NPHP6) gene are a frequent cause of Leber congenital amaurosis. Am. J. Hum. Genet.79(3), 556–561 (2006).
  • Wang H, Den Hollander AI, Moayedi Y et al. Mutations in SPATA7 cause Leber congenital amaurosis and juvenile retinitis pigmentosa. Am. J. Hum. Genet.84(3), 380–387 (2009).
  • Perrault I, Hanein S, Gerard X et al. Spectrum of SPATA7 mutations in Leber congenital amaurosis and delineation of the associated phenotype. Hum. Mutat.31(3), E1241–E1250 (2010).
  • Mackay DS, Ocaka LA, Borman AD et al. Screening of SPATA7 in patients with Leber congenital amaurosis and severe childhood-onset retinal dystrophy reveals disease-causing mutations. Invest. Ophthalmol. Vis. Sci.52(6), 3032–3038 (2011).
  • Sergouniotis PI, Davidson AE, Mackay DS et al. Recessive mutations in KCNJ13, encoding an inwardly rectifying potassium channel subunit, cause Leber congenital amaurosis. Am. J. Hum. Genet.89(1), 183–190 (2011).
  • Stone EM, Cideciyan AV, Aleman TS et al. Variations in NPHP5 in patients with nonsyndromic Leber congenital amaurosis and Senior–Loken syndrome. Arch. Ophthalmol.129(1), 81–87 (2011).
  • Estrada-Cuzcano A, Koenekoop RK, Coppieters F et al.IQCB1 mutations in patients with Leber congenital amaurosis. Invest. Ophthalmol. Vis. Sci.52(2), 834–839 (2011).
  • Wang X, Wang H, Cao M et al. Whole-exome sequencing identifies ALMS1, IQCB1, CNGA3, and MYO7A mutations in patients with Leber congenital amaurosis. Hum. Mutat.32(12), 1450–1459 (2011).
  • Li Y, Wang H, Peng J et al. Mutation survey of known LCA genes and loci in the Saudi Arabian population. Invest. Ophthalmol. Vis. Sci.50(3), 1336–1343 (2009).
  • Seong MW, Kim SY, Yu YS, Hwang JM, Kim JY, Park SS. Molecular characterization of Leber congenital amaurosis in Koreans. Mol. Vis.14, 1429–1436 (2008).
  • Simonelli F, Ziviello C, Testa F et al. Clinical and molecular genetics of Leber’s congenital amaurosis: a multicenter study of Italian patients. Invest. Ophthalmol. Vis. Sci.48(9), 4284–4290 (2007).
  • Sundaresan P, Vijayalakshmi P, Thompson S, Ko AC, Fingert JH, Stone EM. Mutations that are a common cause of Leber congenital amaurosis in Northern America are rare in southern India. Mol. Vis.15, 1781–1787 (2009).
  • Mclean JE, Hamaguchi N, Belenky P, Mortimer SE, Stanton M, Hedstrom L. Inosine 5’-monophosphate dehydrogenase binds nucleic acids in vitro and in vivo. Biochem. J.379(Pt 2), 243–251 (2004).
  • Feng W, Yasumura D, Matthes MT, Lavail MM, Vollrath D. Mertk triggers uptake of photoreceptor outer segments during phagocytosis by cultured retinal pigment epithelial cells. J. Biol. Chem.277(19), 17016–17022 (2002).
  • Chang B, Khanna H, Hawes N et al. In-frame deletion in a novel centrosomal/ciliary protein CEP290/NPHP6 perturbs its interaction with RPGR and results in early-onset retinal degeneration in the rd16 mouse. Hum. Mol. Genet.15(11), 1847–1857 (2006).
  • Grossman GH, Pauer GJ, Narendra U, Hagstrom SA. Tubby-like protein 1 (Tulp1) is required for normal photoreceptor synaptic development. Adv. Exp. Med. Biol.664, 89–96 (2010).
  • Grossman GH, Watson RF, Pauer GJ, Bollinger K, Hagstrom SA. Immunocytochemical evidence of Tulp1-dependent outer segment protein transport pathways in photoreceptor cells. Exp. Eye Res.93, 658–668 (2011).
  • Caberoy NB, Zhou Y, Li W. Tubby and tubby-like protein 1 are new MerTK ligands for phagocytosis. EMBO J.29(23), 3898–3910 (2010).
  • Roepman R, Bernoud-Hubac N, Schick DE et al. The retinitis pigmentosa GTPase regulator (RPGR) interacts with novel transport-like proteins in the outer segments of rod photoreceptors. Hum. Mol. Genet.9(14), 2095–2105 (2000).
  • Azadi S, Molday LL, Molday RS. RD3, the protein associated with Leber congenital amaurosis type 12, is required for guanylate cyclase trafficking in photoreceptor cells. Proc. Natl Acad. Sci. USA107(49), 21158–21163 (2010).
  • Boldt K, Mans DA, Won J et al. Disruption of intraflagellar protein transport in photoreceptor cilia causes Leber congenital amaurosis in humans and mice. J. Clin. Invest.121(6), 2169–2180 (2011).
  • Van De Pavert SA, Kantardzhieva A, Malysheva A et al. Crumbs homologue 1 is required for maintenance of photoreceptor cell polarization and adhesion during light exposure. J. Cell Sci.117(Pt 18), 4169–4177 (2004).
  • Van Rossum AG, Aartsen WM, Meuleman J et al. Pals1/Mpp5 is required for correct localization of Crb1 at the subapical region in polarized Müller glia cells. Hum. Mol. Genet.15(18), 2659–2672 (2006).
  • Karan S, Frederick JM, Baehr W. Novel functions of photoreceptor guanylate cyclases revealed by targeted deletion. Mol. Cell. Biochem.334(1–2), 141–155 (2010).
  • Kirschman LT, Kolandaivelu S, Frederick JM et al. The Leber congenital amaurosis protein, AIPL1, is needed for the viability and functioning of cone photoreceptor cells. Hum. Mol. Genet.19(6), 1076–1087 (2010).
  • Kolandaivelu S, Huang J, Hurley JB, Ramamurthy V. AIPL1, a protein associated with childhood blindness, interacts with alpha-subunit of rod phosphodiesterase (PDE6) and is essential for its proper assembly. J. Biol. Chem.284(45), 30853–30861 (2009).
  • Derst C, Doring F, Preisig-Müller R et al. Partial gene structure and assignment to chromosome 2q37 of the human inwardly rectifying K+ channel (Kir7.1) gene (KCNJ13). Genomics54(3), 560–563 (1998).
  • Ding XQ, Fitzgerald JB, Quiambao AB, Harry CS, Malykhina AP. Molecular pathogenesis of achromatopsia associated with mutations in the cone cyclic nucleotide-gated channel CNGA3 subunit. Adv. Exp. Med. Biol.664, 245–253 (2010).
  • Otto EA, Loeys B, Khanna H et al. Nephrocystin-5, a ciliary IQ domain protein, is mutated in Senior–Loken syndrome and interacts with RPGR and calmodulin. Nat. Genet.37(3), 282–288 (2005).
  • Williams DS, Lopes VS. The many different cellular functions of MYO7A in the retina. Biochem. Soc. Trans.39(5), 1207–1210 (2011).
  • Collin GB, Cyr E, Bronson R et al. Alms1-disrupted mice recapitulate human Alstrom syndrome. Hum. Mol. Genet.14(16), 2323–2333 (2005).
  • Kaplan J. Leber congenital amaurosis: from darkness to spotlight. Ophthalmic Genet.29(3), 92–98 (2008).
  • Dharmaraj SR, Silva ER, Pina AL et al. Mutational analysis and clinical correlation in Leber congenital amaurosis. Ophthalmic Genet.21(3), 135–150 (2000).
  • Walia S, Fishman GA, Jacobson SG et al. Visual acuity in patients with Leber’s congenital amaurosis and early childhood-onset retinitis pigmentosa. Ophthalmology117(6), 1190–1198 (2010).
  • Schuster A, Janecke AR, Wilke R et al. The phenotype of early-onset retinal degeneration in persons with RDH12 mutations. Invest. Ophthalmol. Vis. Sci.48(4), 1824–1831 (2007).
  • Jacobson SG, Cideciyan AV, Aleman TS et al. Human retinal disease from AIPL1 gene mutations: foveal cone loss with minimal macular photoreceptors and rod function remaining. Invest. Ophthalmol. Vis. Sci.52(1), 70–79 (2011).
  • Chung DC, Traboulsi EI. Leber congenital amaurosis: clinical correlations with genotypes, gene therapy trials update, and future directions. J. AAPOS13(6), 587–592 (2009).
  • Galvin JA, Fishman GA, Stone EM, Koenekoop RK. Evaluation of genotype-phenotype associations in Leber congenital amaurosis. Retina25(7), 919–929 (2005).
  • Henderson RH, Mackay DS, Li Z et al. Phenotypic variability in patients with retinal dystrophies due to mutations in CRB1. Br. J. Ophthalmol.95(6), 811–817 (2011).
  • Koenekoop RK, Lopez I, Den Hollander AI, Allikmets R, Cremers FP. Genetic testing for retinal dystrophies and dysfunctions: benefits, dilemmas and solutions. Clin. Experiment. Ophthalmol.35(5), 473–485 (2007).
  • Pasadhika S, Fishman GA, Stone EM et al. Differential macular morphology in patients with RPE65-, CEP290-, GUCY2D-, and AIPL1-related Leber congenital amaurosis. Invest. Ophthalmol. Vis. Sci.51(5), 2608–2614 (2010).
  • McKay GJ, Clarke S, Davis JA, Simpson DA, Silvestri G. Pigmented paravenous chorioretinal atrophy is associated with a mutation within the crumbs homolog 1 (CRB1) gene. Invest. Ophthalmol. Vis. Sci.46(1), 322–328 (2005).
  • Jacobson SG, Cideciyan AV, Aleman TS et al. Crumbs homolog 1 (CRB1) mutations result in a thick human retina with abnormal lamination. Hum. Mol. Genet.12(9), 1073–1078 (2003).
  • Lotery AJ, Jacobson SG, Fishman GA et al. Mutations in the CRB1 gene cause Leber congenital amaurosis. Arch. Ophthalmol.119(3), 415–420 (2001).
  • Den Hollander AI, Heckenlively JR, Van Den Born LI et al. Leber congenital amaurosis and retinitis pigmentosa with Coats-like exudative vasculopathy are associated with mutations in the crumbs homologue 1 (CRB1) gene. Am. J. Hum. Genet.69(1), 198–203 (2001).
  • Cideciyan AV, Aleman TS, Jacobson SG et al. Centrosomal-ciliary gene CEP290/NPHP6 mutations result in blindness with unexpected sparing of photoreceptors and visual brain: implications for therapy of Leber congenital amaurosis. Hum. Mutat.28(11), 1074–1083 (2007).
  • Valverde D, Pereiro I, Vallespin E, Ayuso C, Borrego S, Baiget M. Complexity of phenotype–genotype correlations in Spanish patients with RDH12 mutations. Invest. Ophthalmol. Vis. Sci.50(3), 1065–1068 (2009).
  • Mckibbin M, Ali M, Mohamed MD et al. Genotype–phenotype correlation for Leber congenital amaurosis in northern Pakistan. Arch. Ophthalmol.128(1), 107–113 (2010).
  • Testa F, Surace EM, Rossi S et al. Evaluation of Italian patients with Leber congenital amaurosis due to AIPL1 mutations highlights the potential applicability of gene therapy. Invest. Ophthalmol. Vis. Sci.52(8), 5618–5624 (2011).
  • Khanna H, Davis EE, Murga-Zamalloa CA et al. A common allele in RPGRIP1L is a modifier of retinal degeneration in ciliopathies. Nat. Genet.41(6), 739–745 (2009).
  • Den Hollander AI, Black A, Bennett J, Cremers FP. Lighting a candle in the dark: advances in genetics and gene therapy of recessive retinal dystrophies. J. Clin. Invest.120(9), 3042–3053 (2010).
  • Acland GM, Aguirre GD, Ray J et al. Gene therapy restores vision in a canine model of childhood blindness. Nat. Genet.28(1), 92–95 (2001).
  • Narfstrom K, Katz ML, Bragadottir R et al. Functional and structural recovery of the retina after gene therapy in the RPE65 null mutation dog. Invest. Ophthalmol. Vis. Sci.44(4), 1663–1672 (2003).
  • Acland GM, Aguirre GD, Bennett J et al. Long-term restoration of rod and cone vision by single dose rAAV-mediated gene transfer to the retina in a canine model of childhood blindness. Mol. Ther.12(6), 1072–1082 (2005).
  • Weber M, Rabinowitz J, Provost N et al. Recombinant adeno-associated virus serotype 4 mediates unique and exclusive long-term transduction of retinal pigmented epithelium in rat, dog, and nonhuman primate after subretinal delivery. Mol. Ther.7(6), 774–781 (2003).
  • Jacobson SG, Acland GM, Aguirre GD et al. Safety of recombinant adeno-associated virus type 2-RPE65 vector delivered by ocular subretinal injection. Mol. Ther.13(6), 1074–1084 (2006).
  • Jacobson SG, Boye SL, Aleman TS et al. Safety in nonhuman primates of ocular AAV2-RPE65, a candidate treatment for blindness in Leber congenital amaurosis. Hum. Gene Ther.17(8), 845–858 (2006).
  • Hauswirth WW, Aleman TS, Kaushal S et al. Treatment of Leber congenital amaurosis due to RPE65 mutations by ocular subretinal injection of adeno-associated virus gene vector: short-term results of a Phase I trial. Hum. Gene Ther.19(10), 979–990 (2008).
  • Cideciyan AV. Leber congenital amaurosis due to RPE65 mutations and its treatment with gene therapy. Prog. Retin. Eye Res.29(5), 398–427 (2010).
  • Cideciyan AV, Hauswirth WW, Aleman TS et al. Human RPE65 gene therapy for Leber congenital amaurosis: persistence of early visual improvements and safety at 1 year. Hum. Gene Ther.20(9), 999–1004 (2009).
  • Simonelli F, Maguire AM, Testa F et al. Gene therapy for Leber’s congenital amaurosis is safe and effective through 1.5 years after vector administration. Mol. Ther.18(3), 643–650 (2010).
  • Semple-Rowland SL, Lee NR, Van Hooser JP, Palczewski K, Baehr W. A null mutation in the photoreceptor guanylate cyclase gene causes the retinal degeneration chicken phenotype. Proc. Natl Acad. Sci. USA95(3), 1271–1276 (1998).
  • Williams ML, Coleman JE, Haire SE et al. Lentiviral expression of retinal guanylate cyclase-1 (RetGC1) restores vision in an avian model of childhood blindness. PLoS Med.3(6), e201 (2006).
  • Boye SE, Boye SL, Pang J et al. Functional and behavioral restoration of vision by gene therapy in the guanylate cyclase-1 (GC1) knockout mouse. PLoS One5(6), e11306 (2010).
  • Mihelec M, Pearson RA, Robbie SJ et al. Long-term preservation of cones and improvement in visual function following gene therapy in a mouse model of Leber congenital amaurosis caused by guanylate cyclase-1 deficiency. Hum. Gene Ther.22(10), 1179–1190 (2011).
  • Ramamurthy V, Niemi GA, Reh TA, Hurley JB. Leber congenital amaurosis linked to AIPL1: a mouse model reveals destabilization of cGMP phosphodiesterase. Proc. Natl Acad. Sci. USA101(38), 13897–13902 (2004).
  • Liu X, Bulgakov OV, Wen XH et al. AIPL1, the protein that is defective in Leber congenital amaurosis, is essential for the biosynthesis of retinal rod cGMP phosphodiesterase. Proc. Natl Acad. Sci. USA101(38), 13903–13908 (2004).
  • Sun X, Pawlyk B, Xu X et al. Gene therapy with a promoter targeting both rods and cones rescues retinal degeneration caused by AIPL1 mutations. Gene Ther.17(1), 117–131 (2010).
  • Gerner M, Haribaskar R, Putz M, Czerwitzki J, Walz G, Schafer T. The retinitis pigmentosa GTPase regulator interacting protein 1 (RPGRIP1) links RPGR to the nephronophthisis protein network. Kidney Int.77(10), 891–896 (2010).
  • Won J, Gifford E, Smith RS et al. RPGRIP1 is essential for normal rod photoreceptor outer segment elaboration and morphogenesis. Hum. Mol. Genet.18(22), 4329–4339 (2009).
  • Pawlyk BS, Smith AJ, Buch PK et al. Gene replacement therapy rescues photoreceptor degeneration in a murine model of Leber congenital amaurosis lacking RPGRIP. Invest. Ophthalmol. Vis. Sci.46(9), 3039–3045 (2005).
  • Pawlyk BS, Bulgakov OV, Liu X et al. Replacement gene therapy with a human RPGRIP1 sequence slows photoreceptor degeneration in a murine model of Leber congenital amaurosis. Hum. Gene Ther.21(8), 993–1004 (2010).
  • Jacobson SG, Cideciyan AV, Aleman TS et al. Leber congenital amaurosis caused by an RPGRIP1 mutation shows treatment potential. Ophthalmology114(5), 895–898 (2007).
  • Baye LM, Patrinostro X, Swaminathan S et al. The N-terminal region of centrosomal protein 290 (CEP290) restores vision in a zebrafish model of human blindness. Hum. Mol. Genet.20(8), 1467–1477 (2011).
  • D’Cruz PM, Yasumura D, Weir J et al. Mutation of the receptor tyrosine kinase gene Mertk in the retinal dystrophic RCS rat. Hum. Mol. Genet.9(4), 645–651 (2000).
  • Vollrath D, Feng W, Duncan JL et al. Correction of the retinal dystrophy phenotype of the RCS rat by viral gene transfer of Mertk. Proc. Natl Acad. Sci. USA98(22), 12584–12589 (2001).
  • Tschernutter M, Schlichtenbrede FC, Howe S et al. Long-term preservation of retinal function in the RCS rat model of retinitis pigmentosa following lentivirus-mediated gene therapy. Gene Ther.12(8), 694–701 (2005).
  • Smith AJ, Schlichtenbrede FC, Tschernutter M, Bainbridge JW, Thrasher AJ, Ali RR. AAV-mediated gene transfer slows photoreceptor loss in the RCS rat model of retinitis pigmentosa. Mol. Ther.8(2), 188–195 (2003).
  • Batten ML, Imanishi Y, Tu DC et al. Pharmacological and rAAV gene therapy rescue of visual functions in a blind mouse model of Leber congenital amaurosis. PLoS Med.2(11), e333 (2005).
  • Henderson RH, Waseem N, Searle R et al. An assessment of the apex microarray technology in genotyping patients with Leber congenital amaurosis and early-onset severe retinal dystrophy. Invest. Ophthalmol. Vis. Sci.48(12), 5684–5689 (2007).
  • Song J, Smaoui N, Ayyagari R et al. High-throughput retina-array for screening 93 genes involved in inherited retinal dystrophy. Invest. Ophthalmol. Vis. Sci.52(12), 9053–9060 (2011).
  • Pomares E, Riera M, Permanyer J et al. Comprehensive SNP-chip for retinitis pigmentosa–Leber congenital amaurosis diagnosis: new mutations and detection of mutational founder effects. Eur. J. Hum. Genet.18(1), 118–124 (2010).
  • Simpson DA, Clark GR, Alexander S, Silvestri G, Willoughby CE. Molecular diagnosis for heterogeneous genetic diseases with targeted high-throughput DNA sequencing applied to retinitis pigmentosa. J. Med. Genet.48(3), 145–151 (2011).

Websites

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.