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Translocation breakpoints in three patients with campomelic dysplasia and autosomal sex reversal map more than 130 kb from SOX9

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Abstract

Campomelic dysplasia (CMPD1) and autosomal XY sex reversal (SRA1) are caused by mutations in the SRY-related gene SOX9 on 17q. Unexpectedly, the 17q breakpoints in four CMPD l translocation cases previously analyzed by us and others map 50 kb or more from SOX9. Here, we present clinical, cytogenetic, and molecular data from a new CMPD1/SRA1 patient with t(6; 17) (q14; q24). Fluorescence in situ hybridization has shown that the 17q breakpoint in this case maps to the same region as the breakpoints in the other translocation cases, at least 130 kb from SOX9. Likewise, the breakpoints in two of the previously described cases also map more than 130 kb and, as shown by pulsed field gel electrophoresis analysis, at most 400 kb or 690 kb from SOX9. By using a SOX9 coding sequence polymorphism, expression of both SOX9 alleles has been demonstrated by the reverse transcriptase polymerase chain reaction in lymphoblastoid cells from one of the translocation cases.

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References

  • Anand R, Riley JH, Butler R, Smith JC, Markham AF (1990) A 3.5 genome equivalent multi access YAC library: construction, characterization, screening and storage. Nucleic Acids Res 18: 1951–1956

    Google Scholar 

  • Cattanach BM, Isaacson JH (1965) Genetic control over the inactivation of autosomal genes attached to the X chromosome. Z Vererb 96:313–323

    Google Scholar 

  • Chatters S, Whitecross N (1994) Campomelic dysplasia with sex reversal associated with an apparently balanced paracentric inversion within the long arm of chromosome 17. Clin Cytogenet Bull 2: 12–13

    Google Scholar 

  • Chumakov IM, Le Gall I, Billault A, Ougen P, Soularue P, Guillou S, Rigault P, Bui H, De Tand MF, Barillot E, Abderrahim H, Cherif D, Berger R, Le Paslier D, Cohen D (1992) Isolation of chromosome 21-specific yeast artificial chromosomes from a total human genome library. Nature Genet 1: 222–225

    Google Scholar 

  • Fantes J, Redeker B, Breen M, Boyle S, Brown J, Fletcher J, Jones S, Bickmore W, Fukushima Y, Mannens M, Danes S, Heyningen V van, Hanson I (1995) Aniridia-associated cytogenetic rearrangements suggest that a position effect may cause the mutant phenotype. Hum Mol Genet 4: 415–422

    Google Scholar 

  • Feinberg AP, Vogelstein B (1983) A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem 132: 6–13

    Google Scholar 

  • Foster JW, Dominguez-Steglich MA, Guioli S, Kwok C, Weller PA, Stevanovic M, Weissenbach J, Mansour S, Young ID, Goodfellow PN, Brook JD, Schafer AJ (1994) Campomelic dysplasia and autosomal sex reversal caused by mutations in an SRY-related gene. Nature 372: 525–530

    Google Scholar 

  • Green ED, Olson MV (1990) Systematic screening of yeast artificial-chromosome libraries by use of the polymerase chain reaction. Proc Natl Acad Sci USA 87: 1213–1217

    Google Scholar 

  • Gyapay G, Morissette J, Vignal A, Dib C, Fizames C, Millasseau P, Marc S, Bernardi G, Lathrop M, Weissenbach J (1994) The 1993–94 Généthon human genetic linkage map. Nature Genet 7 (special issue): 246–339

    Google Scholar 

  • Henglein B, Synovzik H, Groitl P, Bornkamm GW, Hartl P, Lipp M (1989) Three breakpoints of variant t(2;8) translocations in Burkitt's lymphoma cells fall within a region 140 kilobases distal from c-myc. Mol Cell Biol 9: 2105–2113

    Google Scholar 

  • Houston CS, Opitz JM, Spranger JW, Macpherson RI, Reed MH, Gilbert EF, Hernnann J, Schinzel A (1983) The campomelic syndrome: review, report of 17 cases, and follow-up on the currently 17-year old boy first reported by Maroteaux et al. in 1971. Am J Med Genet 15: 3–28

    Google Scholar 

  • Inazawa J, Saito H, Ariyama T, Abe T, Nakamura Y (1993) High-resolution cytogenetic mapping of 342 new cosmid markers including 43 RFLP markers on human chromosome 17 by fluorescence in situ hybridization. Genomics 17: 153–162

    Google Scholar 

  • Joos S, Falk MH, Lichter P, Haluska FG, Henglein B, Lenoir GM, Bomkamm GW (1992) Variable breakpoints in Burkitt lymphoma cells with chromosomal t(8;14) translocation separate cmyc and the IgH locus up to serveral hundred kb. Hum Mol Genet 8: 625–632

    Google Scholar 

  • Jordan T, Hanson IM, Zaletayev D, Hodgson S, Prosser J, Seawright A, Hastie N, Heyningen V van (1992) The human PAX6 gene is mutated in two patients with aniridia. Nature Genet 1: 328–332

    Google Scholar 

  • Lengauer C, Green ED, Cremer T (1992) Fluorescence in situ hybridization of YAC clones after Alu-PCR amplification. Genomics 13: 826–828

    Google Scholar 

  • Macpherson RI, Skinner SA, Donnenfeld AE (1989) Acampomelic campomelic dysplasia. Pediatr Radiol 20: 90–93

    Google Scholar 

  • Maraia R, Saal HM, Wangsa D (1991) A chromosome 17q de novo paracentric inversion in a patient with campomelic dysplasia: case report and etiologic hypothesis. Clin Genet 39: 401–408

    Google Scholar 

  • McKusick VA (1994) Mendelian inheritance in man. A catalog of human genes and genetic disorders, 11th edn. Johns Hopkins University Press, Baltimore London, pp 1677–1678

    Google Scholar 

  • Sambrook J, Fritsch EF, Maniatis T (1989) Molecular cloning: a laboratory manual, 2nd edn. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY

    Google Scholar 

  • Tartof KD, Bishop C, Jones M, Hobbs CA, Locke J (1989) Towards an understanding of position effect variegation. Dev Genet 10: 162–176

    Google Scholar 

  • Tommerup N, Schempp W, Meinecke P, Pedersen S, Bolund L, Brandt C, Goodpasture C, Guldberg P, Held KR, Reinwein H, Saugstad OD, Scherer G, Skjeldal O, Toder R, Westvik J, Hagen CB van den, Wolf U (1993) Assignment of an autosomal sex reversal locus (SRA1) and campomelic dysplasia (CMPD1) to 17824.3-825.1. Nature Genet 4: 170–174

    Google Scholar 

  • Townes TM, Behringer RR (1990) Human globin locus activation region (LAR): role in temporal control. Trends Genet 6: 219–223

    Google Scholar 

  • Vortkamp A, Gessler M, Grzeschik K-H (1991)GLI3 zinc-finger gene interrupted by translocations in Greig syndrome families. Nature 352: 539–540

    Google Scholar 

  • Wagner T, Wirth J, Meyer J, Zabel B, Held M, Zimmer J, Pasantes J, Dagna Bricarelli F, Keutel J, Hustert E, Wolf U, Tommerup N, Schempp W, Scherer G (1994) Autosomal sex reversal and campomelic dysplasia are caused by mutations in and around the SRY-related gene SOX9. Cell 79: 1111–1120

    Google Scholar 

  • Wright E, Hargrave MR, Christiansen J, Cooper L, Kun J, Evans T, Gangadharan U, Greenfield A, Koopman P (1995) The Sryrelated gene Sox9 is expressed during chondrogenesis in mouse embryos. Nature Genet 9: 15–20

    Google Scholar 

  • Young ID, Zuccolo JM, Maltby EL, Broderick NJ (1992) Campomelic dysplasia associated with a de novo 2q; 17q reciprocal translocation. J Med Genet 29: 251–252

    Google Scholar 

  • Zhimulev IF, Belyaeva ES, Bolshakov VN, Mal'ceva NI (1989) Position-effect variegation and intercalary heterochromatin: a comparative study. Chromosoma 98: 378–387

    Google Scholar 

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Wirth, J., Wagner, T., Meyer, J. et al. Translocation breakpoints in three patients with campomelic dysplasia and autosomal sex reversal map more than 130 kb from SOX9. Hum Genet 97, 186–193 (1996). https://doi.org/10.1007/BF02265263

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  • DOI: https://doi.org/10.1007/BF02265263

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