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J Med Genet. Feb 2002; 39(2): 91–97.
PMCID: PMC1735035

Identification of a 52 kb deletion downstream of the SOST gene in patients with van Buchem disease


Van Buchem disease is an autosomal recessive skeletal dysplasia characterised by generalised bone overgrowth, predominantly in the skull and mandible. Clinical complications including facial nerve palsy, optic atrophy, and impaired hearing occur in most patients. These features are very similar to those of sclerosteosis and the two conditions are only differentiated by the hand malformations and the tall stature appearing in sclerosteosis. Using an extended Dutch inbred van Buchem family and two inbred sclerosteosis families, we mapped both disease genes to the same region on chromosome 17q12-q21, supporting the hypothesis that van Buchem disease and sclerosteosis are caused by mutations in the same gene. In a previous study, we positionally cloned a novel gene, called SOST, from the linkage interval and identified three different, homozygous mutations in the SOST gene in sclerosteosis patients leading to loss of function of the underlying protein. The present study focuses on the identification of a 52 kb deletion in all patients from the van Buchem family. The deletion, which results from a homologous recombination between Alu sequences, starts approximately 35 kb downstream of the SOST gene. Since no evidence was found for the presence of a gene within the deleted region, we hypothesise that the presence of the deletion leads to a down regulation of the transcription of the SOST gene by a cis regulatory action or a position effect.

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Selected References

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  • Beighton P. Sclerosteosis. J Med Genet. 1988 Mar;25(3):200–203. [PMC free article] [PubMed]
  • VAN BUCHEM FS, HADDERS HN, UBBENS R. An uncommon familial systemic disease of the skeleton: hyperostosis corticalis generalisata familiaris. Acta radiol. 1955 Aug;44(2):109–120. [PubMed]
  • Fosmoe RJ, Holm RS, Hildreth RC. Van Buchem's disease (hyperostosis corticalis generalisata familiaris). A case report. Radiology. 1968 Apr;90(4):771–774. [PubMed]
  • Van Hul W, Balemans W, Van Hul E, Dikkers FG, Obee H, Stokroos RJ, Hildering P, Vanhoenacker F, Van Camp G, Willems PJ. Van Buchem disease (hyperostosis corticalis generalisata) maps to chromosome 17q12-q21. Am J Hum Genet. 1998 Feb;62(2):391–399. [PMC free article] [PubMed]
  • Dixon JM, Cull RE, Gamble P. Two cases of Van Buchem's disease. J Neurol Neurosurg Psychiatry. 1982 Oct;45(10):913–918. [PMC free article] [PubMed]
  • García López A, Luque Piñero M, Medina Varo F. Hiperostosis cortical generalizada (Van Buchem). Rev Clin Esp. 1985 Oct;177(6):293–294. [PubMed]
  • Muiño Míguez A, Moreno Esteban B, González Ramallo V, Molina Quiñones J, Alvarez Hernández J, Lafuente J, Jara Albarrán A. Silla turca vacía parcial en la enfermedad de Van Buchem. Med Clin (Barc) 1986 Nov 22;87(17):719–721. [PubMed]
  • Cook JV, Phelps PD, Chandy J. Van Buchem's disease with classical radiological features and appearances on cranial computed tomography. Br J Radiol. 1989 Jan;62(733):74–77. [PubMed]
  • Bettini R, Sessa V, Mingardi R, Molinari A, Anzani P, Vezzetti V. Iperostosi endostale a trasmissione recessiva (malattia di Van Buchem). Segnalazione di un caso. Recenti Prog Med. 1991 Jan;82(1):24–28. [PubMed]
  • Beighton P, Barnard A, Hamersma H, van der Wouden A. The syndromic status of sclerosteosis and van Buchem disease. Clin Genet. 1984 Feb;25(2):175–181. [PubMed]
  • Stein SA, Witkop C, Hill S, Fallon MD, Viernstein L, Gucer G, McKeever P, Long D, Altman J, Miller NR, et al. Sclerosteosis: neurogenetic and pathophysiologic analysis of an American kinship. Neurology. 1983 Mar;33(3):267–277. [PubMed]
  • Sugiura Y, Yasuhara T. Sclerosteosis. A case report. J Bone Joint Surg Am. 1975 Mar;57(2):273–277. [PubMed]
  • Bueno M, Oliván G, Jiménez A, Garagorri JM, Sarría A, Bueno AL, Bueno M, Jr, Ramos FJ. Sclerosteosis in a Spanish male: first report in a person of Mediterranean origin. J Med Genet. 1994 Dec;31(12):976–977. [PMC free article] [PubMed]
  • Tacconi P, Ferrigno P, Cocco L, Cannas A, Tamburini G, Bergonzi P, Giagheddu M. Sclerosteosis: report of a case in a black African man. Clin Genet. 1998 Jun;53(6):497–501. [PubMed]
  • Balemans W, Van Den Ende J, Freire Paes-Alves A, Dikkers FG, Willems PJ, Vanhoenacker F, de Almeida-Melo N, Alves CF, Stratakis CA, Hill SC, et al. Localization of the gene for sclerosteosis to the van Buchem disease-gene region on chromosome 17q12-q21. Am J Hum Genet. 1999 Jun;64(6):1661–1669. [PMC free article] [PubMed]
  • Balemans W, Ebeling M, Patel N, Van Hul E, Olson P, Dioszegi M, Lacza C, Wuyts W, Van Den Ende J, Willems P, et al. Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST). Hum Mol Genet. 2001 Mar 1;10(5):537–543. [PubMed]
  • Brunkow ME, Gardner JC, Van Ness J, Paeper BW, Kovacevich BR, Proll S, Skonier JE, Zhao L, Sabo PJ, Fu Y, et al. Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein. Am J Hum Genet. 2001 Mar;68(3):577–589. [PMC free article] [PubMed]
  • House JW. Facial nerve grading systems. Laryngoscope. 1983 Aug;93(8):1056–1069. [PubMed]
  • Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403–410. [PubMed]
  • Brody LC, Abel KJ, Castilla LH, Couch FJ, McKinley DR, Yin G, Ho PP, Merajver S, Chandrasekharappa SC, Xu J, et al. Construction of a transcription map surrounding the BRCA1 locus of human chromosome 17. Genomics. 1995 Jan 1;25(1):238–247. [PubMed]
  • Jones KA, Black DM, Brown MA, Griffiths BL, Nicolai HM, Chambers JA, Bonjardim M, Xu CF, Boyd M, McFarlane R, et al. The detailed characterisation of a 400 kb cosmid walk in the BRCA1 region: identification and localisation of 10 genes including a dual-specificity phosphatase. Hum Mol Genet. 1994 Nov;3(11):1927–1934. [PubMed]
  • Friedman LS, Ostermeyer EA, Lynch ED, Welcsh P, Szabo CI, Meza JE, Anderson LA, Dowd P, Lee MK, Rowell SE, et al. 22 genes from chromosome 17q21: cloning, sequencing, and characterization of mutations in breast cancer families and tumors. Genomics. 1995 Jan 1;25(1):256–263. [PubMed]
  • Harteveld KL, Losekoot M, Fodde R, Giordano PC, Bernini LF. The involvement of Alu repeats in recombination events at the alpha-globin gene cluster: characterization of two alphazero-thalassaemia deletion breakpoints. Hum Genet. 1997 Apr;99(4):528–534. [PubMed]
  • Tvrdik T, Marcus S, Hou SM, Fält S, Noori P, Podlutskaja N, Hanefeld F, Strømme P, Lambert B. Molecular characterization of two deletion events involving Alu-sequences, one novel base substitution and two tentative hotspot mutations in the hypoxanthine phosphoribosyltransferase (HPRT) gene in five patients with Lesch-Nyhan syndrome. Hum Genet. 1998 Sep;103(3):311–318. [PubMed]
  • Kleinjan DJ, van Heyningen V. Position effect in human genetic disease. Hum Mol Genet. 1998;7(10):1611–1618. [PubMed]
  • Lauderdale JD, Wilensky JS, Oliver ER, Walton DS, Glaser T. 3' deletions cause aniridia by preventing PAX6 gene expression. Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13755–13759. [PMC free article] [PubMed]
  • Wunderle VM, Critcher R, Hastie N, Goodfellow PN, Schedl A. Deletion of long-range regulatory elements upstream of SOX9 causes campomelic dysplasia. Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10649–10654. [PMC free article] [PubMed]
  • de Kok YJ, Vossenaar ER, Cremers CW, Dahl N, Laporte J, Hu LJ, Lacombe D, Fischel-Ghodsian N, Friedman RA, Parnes LS, et al. Identification of a hot spot for microdeletions in patients with X-linked deafness type 3 (DFN3) 900 kb proximal to the DFN3 gene POU3F4. Hum Mol Genet. 1996 Sep;5(9):1229–1235. [PubMed]
  • Loots GG, Locksley RM, Blankespoor CM, Wang ZE, Miller W, Rubin EM, Frazer KA. Identification of a coordinate regulator of interleukins 4, 13, and 5 by cross-species sequence comparisons. Science. 2000 Apr 7;288(5463):136–140. [PubMed]
  • Hardison RC. Conserved noncoding sequences are reliable guides to regulatory elements. Trends Genet. 2000 Sep;16(9):369–372. [PubMed]

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