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A novel mutation (967−970+2)delAAAGGT in the choroideremia gene found in a Japanese family and related clinical findings

  • Clinical Investigation
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Abstract

Purpose

To investigate the choroideremia (CHM) gene of one affected male and one obligate carrier in a Japanese family with choroideremia, and to characterize the related clinical features.

Methods

We examined one affected man and one carrier woman from a Japanese family. Genomic DNA was extracted from leukocytes of peripheral blood collected from the affected man and his daughter, who is an obligate carrier of choroideremia. Exons 1–15 of the CHM gene were amplified by polymerase chain reaction (PCR) and directly sequenced. We performed ophthalmic examinations including best-corrected visual acuity, slit-lamp examination, fundus examination, electroretinography, and Goldmann perimetry.

Results

A novel (967−970+2)delAAAGGT mutation was detected in the CHM gene. The affected man was hemizygous and had night-blindness, chorioretinal atrophy spreading from the posterior pole to the mid-periphery, and bareness of the sclera. His daughter was a heterozygous carrier who had chorioretinal atrophy and mottled appearance of the retinal pigment epithelium.

Conclusion

A novel (967−970+2)delAAAGGT mutation existed in the CHM gene of a Japanese family with choroideremia.

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References

  1. Cremers FPM, van de Pol DJR, van Kerkhoff LPM, Wieringa B, Ropers HH. Cloning of a gene that is rearranged in patients with choroideremia. Nature 1990;347:674–677.

    Article  CAS  PubMed  Google Scholar 

  2. Merry DE, Jänne PA, Landers JE, Lewis RA, Nussbaum RL. Isolation of a candidate gene for choroideremia. Proc Natl Acad Sci U S A 1992;89:2135–2139.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. van Bokhoven H, van den Hurk JA, Bogerd L, et al. Cloning and characterization of the human choroideremia gene. Hum Mol Genet 1994;3:1041–1046.

    Article  PubMed  Google Scholar 

  4. Andres DA, Seabra MC, Brown MS, et al. cDNA cloning of component A of Rab geranylgeranyl transferase and demonstration of its role as a Rab escort protein. Cell 1993;73:1091–1099.

    Article  CAS  PubMed  Google Scholar 

  5. Seabra MC, Brown MS, Goldstein JL. Retinal degeneration in choroideremia: deficiency of rab geranylgeranyl transferase. Science 1993;259:377–381.

    Article  CAS  PubMed  Google Scholar 

  6. Hayakawa M, Fujiki K, Hotta Y, et al. Visual impairment and REP1 gene mutations in Japanese choroideremia patients. Ophthalmic Genet 1999;20:107–115.

    Article  CAS  PubMed  Google Scholar 

  7. Sankila EM, Tolvanen R, van den Hurk JA, Cremers FPM, de la Chapelle A. Aberrant splicing of the CHM gene is a significant cause of choroideremia. Nat Genet 1992;1:109–113.

    Article  CAS  PubMed  Google Scholar 

  8. van den Hurk JA, van de Pol TJ, Molloy CM, et al. Detection and characterization of point mutations in the choroideremia candidate gene by PCR-SSCP analysis and direct DNA sequencing. Am J Hum Genet 1992;50:1195–1202.

    PubMed  PubMed Central  Google Scholar 

  9. van Bokhoven H, Schwartz M, Andréasson S, et al. Mutation spectrum in the CHM gene of Danish and Swedish choroideremia patients. Hum Mol Genet 1994;3:1047–1051.

    Article  PubMed  Google Scholar 

  10. Ponjavic V, Abrahamson M, Andreasson S, et al. Phenotype variations within a choroideremia family lacking the entire CHM gene. Ophthalmic Genet 1995;16:143–150.

    Article  CAS  PubMed  Google Scholar 

  11. Forsythe P, Maguire A, Fujita R, Moen C, Swaroop A, Bennett J. A carboxy-terminal truncation of 99 amino acids resulting from a novel mutation (Arg555→ stop) in the CHM gene leads to choroideremia Exp Eye Res 1997;64:487–490.

    Article  CAS  PubMed  Google Scholar 

  12. van den Hurk JA, Schwartz M, van Bokhoven H, et al. Molecular basis of choroideremia (CHM): mutations involving the Rab escort protein-1(REP1) gene. Hum Mutat 1997;9:110–117.

    Article  PubMed  Google Scholar 

  13. Hotta Y, Fujiki K, Hayakawa M, et al. A hemizygous A to CC base change of the CHM gene causing choroideremia associated with pinealoma. Graefes Arch Clin Exp Ophthalmol 1997;235:653–655.

    Article  CAS  PubMed  Google Scholar 

  14. Fujiki K, Hotta Y, Hayakawa M, et al. REP1 gene mutations in Japanese patients with choroideremia. Graefes Arch Clin Exp Ophthalmol 1999;237:735–740.

    Article  CAS  PubMed  Google Scholar 

  15. Ohba N. Introduction to genetics in ophthalmology, value of family studies. Jpn J Ophthalmol 2000;44:320–321.

    Article  CAS  PubMed  Google Scholar 

  16. McTaggart KE, Tran M, Mah DY, Lai SW, Nesslinger NJ, MacDonald IM. Mutational analysis of patients with the diagnosis of choroideremia. Hum Mutat 2002;20:189–196.

    Article  CAS  PubMed  Google Scholar 

  17. Itabashi T, Wada Y, Kawamura M, Sato H, Tamai M. Clinical features of Japanese families with a 402delT or a 555–556delAG mutation in choroideremia gene. Retina 2004;24:940–945.

    Article  PubMed  Google Scholar 

  18. Marmor MF, Arden GB, Nilson SEG, Zrenner E. Standard for clinical electroretinography. Arch Ophthalmol 1989;107:816–819.

    Article  Google Scholar 

  19. Marmor MF, Holder GE, Seeliger MW, Yamamoto S. Standard for clinical electroretinography (2004 update). Doc Ophthalmol 2004;108:107–114

    Article  PubMed  Google Scholar 

  20. Nakazawa M, Kikawa-Araki E, Shiono T, Tamai M. Analysis of rhodopsin gene in patients with retinitis pigmentosa using allelespecific polymerase chain reaction. Jpn J Ophthalmol 1991;35:386–393.

    CAS  PubMed  Google Scholar 

  21. Roberts MF, Fishman GA, Roberts DK, et al. Retrospective, longitudinal, and cross sectional study of visual acuity impairment in choroideremia. Br J Ophthalmol 2002;86:658–662.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Francois J. Heredity of the choroidal dystrophies. Adv Ophthalmol 1978;35:1–25.

    CAS  PubMed  Google Scholar 

  23. Majid MA, Horsborough B, Gray RH. Unusual macular findings in a known choroideremia carrier. Eye 1998;12:740–741.

    Article  PubMed  Google Scholar 

  24. Endo K, Yuzawa M, Ohba N. Choroideremia associated with subretinal neovascular membrane. Acta Ophthalmol Scand 2000;78:483–486.

    Article  CAS  PubMed  Google Scholar 

  25. Renner AB, Kellner U, Cropp E, et al. Choroideremia: variability of clinical and electrophysiological characteristics and first report of a negative electroretinogram. Ophthalmology 2006;113:2066–2073.

    Article  PubMed  Google Scholar 

  26. Potter MJ, Wong E, Szabo SM, McTaggart KE. Clinical findings in a carrier of a new mutation in the choroideremia gene. Ophthalmology 2004;111:1905–1909.

    Article  PubMed  Google Scholar 

  27. Lyon MF. Gene action in the X-chromosome of the mouse (Mus musculus L.). Nature 1961;190:372–373.

    Article  CAS  PubMed  Google Scholar 

  28. Retina International’s Scientific Newsletter. Mutation database: mutations of the Rab Escort Protein 1. http://www.retinainternational.org/sci-news/repmut.htm

  29. van den Hurk JAJM, Hendriks W, van de Pol DJR, Oerlemans F, et al. Mouse choroideremia gene mutation cases photoreceptor cell degeneration and is not transmitted through the female germline. Hum Mol Genet 1997;6:851–858.

    Article  PubMed  Google Scholar 

  30. Tolmachova T, Anders R, Abrink M, et al. Independent degeneration of photoreceptors and retinal pigment epithelium in conditional knockout mouse models of choroideremia. J Clin Invest 2006;116:386–394.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Starr CJ, Kappler JA, Chan DK, Kollmar R, Hudspeth AJ. Mutant of the zebrafish choroideremia gene encoding Rab escort protein 1 devastates hair cells. Proc Natl Acad Sci U S A 2004;101:2572–2577.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Perkins BD, Bilotta J. Mutaion of the zebrafish choroideremia gene (Rab escort protein1) causes photoreceptor degeneration and loss of visual function [ARVO e-abstract]. Invest Ophthalmol Vis Sci 2006;47:4557.

    Google Scholar 

  33. Krock BL, Bilotta J, Perkins BD. Noncell-autonomous photoreceptor degeneration in a zebrafish model of choroideremia. Proc Natl Acad Sci U S A 2007;104:4600–4605.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Mura M, Sereda CBS, Jablonski MM, MacDonald IM, Lannaccone A. Clinical and functional findings in choroideremia due to complete deletion of the CHM gene. Arch Ophthalmol 2007;125:1107–1113.

    Article  CAS  PubMed  Google Scholar 

  35. Abe T, Yoshida M, Wakusawa R, et al. Iris pigment epithelial cell transplantation for degenerative retinal diseases. Prog Retin Eye Res 2007;26:302–321.

    Article  CAS  PubMed  Google Scholar 

  36. Preising MN. Pooled Sample Homoallelity Testing (PSHT): Ein neues Verfahren zur Genlokalisation bei autosomal rezessiven und X-gekoppelten Erkrankungen. 1999.

  37. Vnencak Jones CI, Manning SS, Phillips JA, Maumenee-Hussels IE, Garrett C. Detection of heterogenous choroideremia mutations in non-Scandinavian patient using dideoxyfingerprinting. Am J Hum Genet 1996;59:A292.

    Google Scholar 

  38. Schwartz M, Rosenberg T, van den Hurk JA, van de Pol DJ, Cremers FP. Identification of mutations in Danish choroideremia families. Hum Mutat 1993;2:43–47.

    Article  CAS  PubMed  Google Scholar 

  39. Beaufrere L, Tuffery S, Hamel C, et al. The protein truncation test (PTT) as a method of detection for choroideremia mutations. Exp Eye Res 1997;65:849–854.

    Article  CAS  PubMed  Google Scholar 

  40. McTaggart KE, Mah DY, Haney P, et al. Identification of REP-1 gene mutations in families diagnosed with choroideremia. Am J Hum Genet 1998;63:A373.

    Google Scholar 

  41. Nesslinger N, Mitchell G, Strasberg P, MacDonald IM. Mutation analysis in Canadian families with choroideremia. Ophthalmic Genet 1996;17:47–52.

    Article  CAS  PubMed  Google Scholar 

  42. Preising M, Pawlowitzki IH. Molecular screening of exons A1, A2, and A3 in 41 unrelated males with choroideremia. Invest Ophthalmol Vis Sci 1993;34:1463.

    Google Scholar 

  43. Fujiki K, Hotta Y, Hayakawa M, et al. REP-1 gene mutations in Japanese patients with choroideremia. Invest Ophthalmol Vis Sci 1998;39:S294.

    Google Scholar 

  44. Küsters U, Preising MN, Lorenz B, Pawlowitzki IH. Characterization of a novel partial deletion of the choroideremia gene. Invest Ophthalmol Vis Sci 1996;37:S107.

    Google Scholar 

  45. Trujillo MJ, Sanz R, Rodriguez de Alba M, et al. First mutation (S340X) in choroideremia gene in a spanish family. Hum Mutat Online 1998.

  46. Donnelly P, Menet H, Fouanon C, Herbert O, Moisan JP, Le Roux MG, Pascal O. Missense mutation in the choroideremia gene. Hum Mol Genet 1994;3:1017.

    Article  CAS  PubMed  Google Scholar 

  47. Beaufrere L, Rieu S, Hache JC, et al. Altered rep-1 expression due to substitution at positin +3 of the IVS13 splice-donor site of choroideremia (CHM) gene. Curr Eye Res 1998;17:726–729.

    CAS  PubMed  Google Scholar 

  48. Presing MN, Pawlowitzki IH. Evaluation of a splice site mutation in Intron 14 of the choroideremia gene. Invest Ophthalmol Vis Sci 1996;37:S107.

    Google Scholar 

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Authors and Affiliations

  1. Department of Ophthalmology, Juntendo University School of Medicine, Tokyo, Japan

    Yutaka Iino, Takuro Fujimaki, Keiko Fujiki & Akira Murakami

Authors
  1. Yutaka Iino
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  2. Takuro Fujimaki
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  3. Keiko Fujiki
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  4. Akira Murakami
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Corresponding author

Correspondence to Yutaka Iino.

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Cite this article

Iino, Y., Fujimaki, T., Fujiki, K. et al. A novel mutation (967−970+2)delAAAGGT in the choroideremia gene found in a Japanese family and related clinical findings. Jpn J Ophthalmol 52, 289–297 (2008). https://doi.org/10.1007/s10384-008-0564-4

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  • DOI: https://doi.org/10.1007/s10384-008-0564-4

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