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Hereditary Eye Disease in Ningxia Hui Autonomous Region of China

  • Weining Rong
  • Huiping Li
  • Xunlun Sheng
Chapter
Part of the Essentials in Ophthalmology book series (ESSENTIALS)

Abstract

Ningxia Hui Autonomous Region is the main gathering region of Hui nationality in China. Because of unique geographical environment and national characteristics, the incidence of hereditary eye disease is higher in Ningxia Region. From 2010 to 2017, our research team collected 230 pedigrees and 268 sporadic patients with monogenic hereditary eye disease, including 210 pedigrees and 250 sporadic patients with hereditary retinal diseases. Among these pedigrees, 89 (42%) families reported a family history of consanguinity. We carried genetic research on 113 pedigrees and 154 sporadic patients with hereditary retinal diseases. The disease-causing mutations were identified in 66 pedigrees and 69 sporadic patients. Total 63 related disease-causing genes were involved. Four new disease-causing genes were discovered through whole exome sequencing combined with a series of cell experiments and animal experiments, including GUCA1A gene that causes central areolar choroidal dystrophy, CCT2 gene that causes Leber congenital amaurosis, CEP78 gene that causes Usher syndrome, and PRPF4 gene that causes autosomal dominant retinitis pigmentosa. Through whole exome sequencing, we confirmed the clinical diagnosis of combined Marfan syndrome with X-linked hypophosphatemia in a pedigree with complex phenotypes. The homozygous mutation of BEST1 gene was found in a consanguineous family with complicated phenotype, and the diagnosis of autosomal recessive bestrophinopathy (ARB) was made.

Keywords

Ningxia Ocular disease Genetic Gene Mutation Consanguineous marriage 

Notes

Conflict of Interest

The authors declare that they have no conflict of interest.

Compliance with Ethical Requirements

In our study, all procedures followed were in accordance with the ethical standards of the Committee of Ningxia People’s Hospital on human experimentation and with the Helsinki Declaration of 1975, as revised in 2010.

References

  1. 1.
    Waardenburg PJ. Angio-sclerose familial de la choroid. J Genet Hum. 1952;1:83–93.PubMedGoogle Scholar
  2. 2.
    Boon CJF, Klevering BJ, Cremers FPM, Zonneveld-Vrieling MN, Theelen T, Den Hollander AI, Hoyng CB. Central areolar choroidal dystrophy. Ophthalmology. 2009;116(4):771–82.CrossRefGoogle Scholar
  3. 3.
    Hoyng CB, Deutman AF. The development of central areolar choroidal dystrophy. Graefes Arch Clin Exp Ophthalmol. 1996;234(2):87–93.CrossRefGoogle Scholar
  4. 4.
    Smailhodzic D, Fleckenstein M, Theelen T, et al. Central areolar choroidal dystrophy (CACD) and age-related macular degeneration (AMD): differentiating characteristics in multimodal imaging. Invest Ophthalmol Vis Sci. 2011;52(12):8908–18.CrossRefGoogle Scholar
  5. 5.
    Keilhauer CN, Meigen T, Stöhr H, Weber BH. Late-onset central areolar choroidal dystrophy caused by a heterozygous frame-shift mutation affecting codon 307 of the peripherin/RDS gene. Ophthalmic Genet. 2006 Dec;27(4):139–44.CrossRefGoogle Scholar
  6. 6.
    Ouechtati F, Belhadj Tahar O, Mhenni A, Chakroun S, Chouchene I, Oueslati S, Rebai A, Abdelhak S, Jeddi-Blouza A. Central areolar choroidal dystrophy associated with inherited drusen in a multigeneration Tunisian family: exclusion of the PRPH2 gene and the 17p13 locus. J Hum Genet. 2009;54(10):589–94.CrossRefGoogle Scholar
  7. 7.
    Klevering BJ, van Driel M, van Hogerwou AJ, van De Pol DJ, Deutman AF, Pinckers AJ, Cremers FP, Hoyng CB. Central areolar choroidal dystrophy associated with dominantly inherited drusen. Br J Ophthalmol. 2002;86(1):91–6.CrossRefGoogle Scholar
  8. 8.
    Prokofyeva E, Wilke R, Lotz G, Troeger E, Strasser T, Zrenner E. An epidemiological approach for the estimation of disease onset in Central Europe in central and peripheral monogenic retinal dystrophies. Graefes Arch Clin Exp Ophthalmol. 2009;247(7):885–94.CrossRefGoogle Scholar
  9. 9.
    Chen X, Sheng X, Zhuang W, Sun X, Liu G, Shi X, Huang G, Mei Y, Li Y, Pan X, Liu Y, Li Z, Zhao Q, Yan B, Zhao C. GUCA1A mutation causes maculopathy in a five-generation family with a wide spectrum of severity. Genet Med. 2017;19(8):945–54.CrossRefGoogle Scholar
  10. 10.
    Keen TJ, Inglehearn CF. Mutations and polymorphisms in the human peripherin-RDS gene and their involvement in inherited retinal degeneration. Hum Mutat. 1996;8(4):297–303.CrossRefGoogle Scholar
  11. 11.
    Yanagihashi S, Nakazawa M, Kurotaki J, Sato M, Miyagawa Y, Ohguro H. Autosomal dominant central areolar choroidal dystrophy and a novel Arg195Leu mutation in the peripherin/RDS gene. Arch Ophthalmol. 2003;121(10):1458–61.CrossRefGoogle Scholar
  12. 12.
    Hughes AE, Meng W, Lotery AJ, Bradley DT. A novel GUCY2D mutation, V933A, causes central areolar choroidal dystrophy. Invest Ophthalmol Vis Sci. 2012;53(8):4748–53.  https://doi.org/10.1167/iovs.12-10061.CrossRefPubMedGoogle Scholar
  13. 13.
    Wells J, Wroblewski J, Keen J, Inglehearn C, Jubb C, Eckstein A, Jay M, Arden G, Bhattacharya S, Fitzke F, Bird A. Mutations in the human retinal degeneration slow (RDS) gene can cause either retinitis pigmentosa or macular dystrophy. Nat Genet. 1993;3:213–8.CrossRefGoogle Scholar
  14. 14.
    Reig C, Serra A, Gean E, Vidal M, Arumi J, De la Calzada MD, Antich J, Carballo M. A point mutation in the RDS-peripherin gene in a Spanish family with central areolar choroidal dystrophy. Ophthalmic Genet. 1995;16:39–44.CrossRefGoogle Scholar
  15. 15.
    Hoyng CB, Heutink P, Testers L, Pinckers A, Deutman AF, Oostra BA. Autosomal dominant central areolar choroidal dystrophy caused by a mutation in codon 142 in the peripherin/RDS gene. Am J Ophthalmol. 1996;121:623–9.CrossRefGoogle Scholar
  16. 16.
    Trujillo MJ, Bueno J, Osorio A, et al. Three novel RDS-peripherin mutations (689delT, 857del17, G208D) in Spanish families affected with autosomal dominant retinal degenerations: mutations in brief no 147 online. Hum Mutat. 1998;12:70.CrossRefGoogle Scholar
  17. 17.
    Renner AB, Fiebig BS, Weber BH, Wissinger B, Andreasson S, Gal A, Cropp E, Kohl S, Kellner U. Phenotypic variability and long-term follow-up of patients with known and novel PRPH2/RDS gene mutations. Am J Ophthalmol. 2009;147(3):518–30.CrossRefGoogle Scholar
  18. 18.
    Conley SM, Stuck MW, Burnett JL, et al. Insights into the mechanisms of macular degeneration associated with the R172W mutation in RDS. Hum Mol Genet. 2014;23:3102–14.CrossRefGoogle Scholar
  19. 19.
    Michaelides M, Holder GE, Bradshaw K, Hunt DM, Moore AT. Cone-rod dystrophy, intrafamilial variability, and incomplete penetrance associated with the R172W mutation in the peripherin/RDS gene. Ophthalmology. 2005;112:1592–8.CrossRefGoogle Scholar
  20. 20.
    Khani SC, Karoukis AJ, Young JE, Ambasudhan R, Burch T, Stockton R, Lewis RA, Sulliva LS, Daiger SP, Reichel E, Ayyagari R. Late-onset autosomal dominant macular dystrophy with choroidal neovascularization and nonexudative maculopathy associated with mutation in the RDS gene. Invest Ophthalmol Vis Sci. 2003;44:3570–7.CrossRefGoogle Scholar
  21. 21.
    Hunt DM, Buch P, Michaelides M. Guanylate cyclases and associated activator proteins in retinal disease. Mol Cell Biochem. 2010;334(1-2):157–68.CrossRefGoogle Scholar
  22. 22.
    Vocke F, Weisschuh N, Marino V, Malfatti S, Jacobson SG, Reiff CM, Dell’Orco D, Koch KW. Dysfunction of cGMP signalling in photoreceptors by a macular dystrophy-related mutation in the calcium sensor GCAP1. Hum Mol Genet. 2017;26(1):133–44.PubMedGoogle Scholar
  23. 23.
    Kaplan J. Leber congenital amaurosis: from darkness to spotlight. Ophthalmic Genet. 2008;29:92–8.  https://doi.org/10.1080/13816810802232768.CrossRefPubMedGoogle Scholar
  24. 24.
    Koenekoop RK. An overview of Leber congenital amaurosis: a model to understand human retinal development. Surv Ophthalmol. 2004;49:379–98.  https://doi.org/10.1016/j.survophthal.2004.04.003.CrossRefPubMedGoogle Scholar
  25. 25.
    Hope CI, Bundey S, Proops D, et al. Usher syndrome in the city ofBirmingham–prevalence and clinical classification. Br J Ophthalmol. 1997;81:46–53.CrossRefGoogle Scholar
  26. 26.
    Rosenberg T, Haim M, Hauch AM, et al. The prevalence of Usher syndromeand other retinal dystrophy-hearing impairment associations. Clin Genet. 1997;51:314–21.CrossRefGoogle Scholar
  27. 27.
    Espinós C, Millán JM, Beneyto M, et al. Epidemiology of Usher syndrome inValencia and Spain. Community Genet. 1998;1:223–8.PubMedGoogle Scholar
  28. 28.
    Nakanishi H, Ohtsubo M, Iwasaki S, et al. Identification of 11 novel mutations in USH2A among Japanese patients with Ushersyndrome type 2. Clin Genet. 2009;76:383–91.CrossRefGoogle Scholar
  29. 29.
    Bonnet C, Grati M, Marlin S, et al. Complete exon sequencing of all known Ushersyndrome genes greatly improves molecular diagnosis. Orphanet J Rare Dis. 2011;6:21.CrossRefGoogle Scholar
  30. 30.
    Jiang L, Liang X, Li Y, et al. Comprehensive molecular diagnosis of 67 Chinese Usher syndromeprobands: high rate of ethnicity specific mutations in Chinese USH patients. Orphanet J Rare Dis. 2015;10:110.CrossRefGoogle Scholar
  31. 31.
    Carrillo J, Martinez P, Solera J, et al. High resolution melting analysis for the identification of novelmutations inDKC1andTERTgenes in patients with dyskeratosis congenita. Blood Cells Mol Dis. 2012;49:140–6.CrossRefGoogle Scholar
  32. 32.
    Chizzolini M, Galan A, Milan E, et al. Goodepidemiologic practice in retinitis pigmentosa: from phenotyping to biobanking. Curr Genomics. 2011;12:260–6.CrossRefGoogle Scholar
  33. 33.
    Collin RW, Safieh C, Littink KW, et al. Mutations in C2ORF71 cause autosomal-recessive retinitis pigmentosa. Am J Hum Genet. 2010;86:783–8.CrossRefGoogle Scholar
  34. 34.
    Hartong DT, Berson EL, Dryja TP. Retinitis pigmentosa. Lancet. 2006;368:1795–809.CrossRefGoogle Scholar
  35. 35.
    von Kodolitsch Y, Robinson PN. Marfan syndrome: an update of genetics, medical and surgical management. Heart. 2007;93:755–60.CrossRefGoogle Scholar
  36. 36.
    Dietz HCMarfan Syndrome. Gene Reviews. University of Washington, Seattle. 1993 http://www.ncbi.nlm.nih.gov/books/NBK1335/
  37. 37.
    Cheon CK, Lee HS, Kim SY, et al. A novelde novo mutation within PHEX gene in a young girl with hypophosphatemic rickets and review of literature. Ann Pediatr Endocrinol Metab. 2014;19:36–41.CrossRefGoogle Scholar
  38. 38.
    Ruppe MD. X-linked hypophosphatemia. Gene Reviews. University of Washington, Seattle. 1993. http://www.ncbi.nlm.nih.gov/books/NBK83985/
  39. 39.
    Burgess R, Millar ID, Leroy BP, et al. Biallelic mutation of BEST1 causes a distinct retinopathy in humans. Am J Hum Genet. 2008;82:19–31.CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Weining Rong
    • 1
  • Huiping Li
    • 1
  • Xunlun Sheng
    • 1
  1. 1.Ningxia Eye Hospital, Ningxia People’s HospitalNingxiaChina

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