Identification of a 52 kb deletion downstream of the SOST gene in patients with van Buchem disease
Open accessAbstract
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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Mutations in genes that have highly enriched expression in osteocytes cause rare bone and mineral disorders.
“Mutations in genes that have highly enriched expression in osteocytes cause rare bone and mineral disorders.”
From Osteocyte transcriptome mapping identifies a molecular landscape controlling skeletal homeostasis and susceptibility to skeletal disease (2021) · cites this paper as [19]
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Altschul, S. F., Gish, W., Miller, W., Myers, E. W., & Lipman, D. J. (1990) · Journal of Molecular Biology · doi:10.1006/jmbi.1990.9999 · Cited by 98,669 · see citing works
Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST)
Balemans, W. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.5.537 · Cited by 1,147 · see citing works
Self-citationBrunkow, M. E., Gardner, J. C., Van Ness, J., Paeper, B. W., Kovacevich, B. R., Proll, S., Skonier, J. E., Zhao, L., Sabo, P. J., Fu, Y.-H., et al. (2001) · The American Journal of Human Genetics · doi:10.1086/318811 · Cited by 1,011 · see citing works
Loots, G. G., Locksley, R. M., Blankespoor, C. M., Wang, Z., Miller, W., Rubin, E. M., & Frazer, K. A. (2000) · Science · doi:10.1126/science.288.5463.136 · Cited by 783 · see citing works
Sonnhammer, E. L. L., & Durbin, R. M. (1995) · Gene · doi:10.1016/0378-1119(95)00714-8 · Cited by 766 · see citing works
House, J. W. (1983) · The Laryngoscope · doi:10.1288/00005537-198308000-00016 · Cited by 441 · see citing works
Conserved noncoding sequences are reliable guides to regulatory elements
Hardison, R. C. (2000) · Trends in Genetics · doi:10.1016/s0168-9525(00)02081-3 · Cited by 418 · see citing works
Position effect in human genetic disease
Kleinjan, D. A. (1998) · Human Molecular Genetics · doi:10.1093/hmg/7.10.1611 · Cited by 370 · see citing works
3′ deletions cause aniridia by preventing PAX6 gene expression
Lauderdale, J. D., Wilensky, J. S., Oliver, E. R., Walton, D. S., & Glaser, T. M. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.240398797 · Cited by 164 · see citing works
de Kok, Y. (1996) · Human Molecular Genetics · doi:10.1093/hmg/5.9.1229 · Cited by 164 · see citing works
Deletion of long-range regulatory elements upstream of SOX9 causes campomelic dysplasia
Wunderle, V. M., Critcher, R., Hastie, N. D., Goodfellow, P. N., & Schedl, A. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.18.10649 · Cited by 159 · see citing works
Van Buchem Disease (Hyperostosis Corticalis Generalisata) Maps to Chromosome 17q12-q21
Hul, W. V., Balemans, W., Hul, E. V., Dikkers, F. G., Obee, H., Stokroos, R. J., Hildering, P., Vanhoenacker, F. M. H. M., Camp, G. V., & Willems, P. J. (1998) · The American Journal of Human Genetics · doi:10.1086/301721 · Cited by 157 · see citing works
Self-citationvan Buchem, F. S. P., Hadders, H. N., & Ubbens, R. (1955) · Acta Radiologica · doi:10.3109/00016925509170789 · Cited by 148 · see citing works
Balemans, W., van den Ende, J., Paes-Alves, A. F., Dikkers, F. G., Willems, P. J., Vanhoenacker, F. M. H. M., de Melo, N. A., Alves, C. F., Stratakis, C. A., Hill, S. C., et al. (1999) · The American Journal of Human Genetics · doi:10.1086/302416 · Cited by 135 · see citing works
Self-citationThe syndromic status of sclerosteosis and van Buchem disease
Beighton, P., Barnard, A., Hamersma, H. A., & van der Wouden, A. (1984) · Clinical Genetics · doi:10.1111/j.1399-0004.1984.tb00481.x · Cited by 133 · see citing works
Stein, S. A., Witkop, C. J., Hill, S. C., Fallon, M. D., Viernstein, L. J., Gucer, G., McKeever, P. E., Long, D. M., Altman, J., Miller, N. R., et al. (1983) · Neurology · doi:10.1212/wnl.33.3.267 · Cited by 96 · see citing works
Beighton, P. (1988) · Journal of Medical Genetics · doi:10.1136/jmg.25.3.200 · Cited by 86 · see citing works
Harteveld, K. L., Losekoot, M., Fodde, R., et al. (1997) · Human Genetics · doi:10.1007/s004390050401 · Cited by 68 · see citing works
Construction of a transcription map surrounding the BRCA1 locus of human chromosome 17
Brody, L. C., Abel, K. J., Castilla, L. H., Couch, F. J., McKinley, D. R., Yin, G., Ho, P. P.-K., Merajver, S. D., Chandrasekharappa, S. C., Xu, J., et al. (1995) · Genomics · doi:10.1016/0888-7543(95)80131-5 · Cited by 63 · see citing works
Sugiura, Y., & Yasuhara, T. (1975) · Journal of Bone and Joint Surgery · doi:10.2106/00004623-197557020-00026 · Cited by 60 · see citing works
Congenital Anomalies of the Face and Associated Structures
Scott, J. E. (1962) · Europe PMC (PubMed Central) · Cited by 49 · see citing works
Friedman, L. S., Ostermeyer, E. A., Lynch, E. D., et al. (1995) · Genomics · doi:10.1016/0888-7543(95)80133-7 · Cited by 48 · see citing works
Higinbotham, N. L., & Alexander, S. F. (1941) · The American Journal of Surgery · doi:10.1016/s0002-9610(41)90660-8 · Cited by 44 · see citing works
Two cases of Van Buchem's disease.
Dixon, J. M., Cull, R. E., & Gamble, P. (1982) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.45.10.913 · Cited by 39 · see citing works
Sclerosteosis in a Spanish male: first report in a person of Mediterranean origin.
Bueno, M., Oliván-Gonzalvo, G., Jiménez, A., Garagorri, J. M., Sarría, A., Bueno, A. L., Bueno, M., & Ramos, F. J. (1994) · Journal of Medical Genetics · doi:10.1136/jmg.31.12.976 · Cited by 34 · see citing works
Tvrdik, T., Marcus, S., Hou, S., et al. (1998) · Human Genetics · doi:10.1007/s004390050822 · Cited by 31 · see citing works
Sclerosteosis: report of a case in a black African man
Tacconi, P., Ferrigno, P., Cocco, L., Carinas, A., Tamburini, G., Bergonzi, P., & Giagheddu, M. (1998) · Clinical Genetics · doi:10.1111/j.1399-0004.1998.tb02603.x · Cited by 28 · see citing works
Albers-Schönberg Disease—A Family Survey
Kelley, C. H., & Lawlah, J. W. (1946) · Radiology · doi:10.1148/47.5.507 · Cited by 27 · see citing works
Van Buchem's Disease (Hyperostosis Corticalis Generalisata Familiaris)
Fosmoe, R. J., Holm, R. S., & Hildreth, R. C. (1968) · Radiology · doi:10.1148/90.4.771 · Cited by 24 · see citing works
Fryns, J. P., & BERGHE, H. V. D. (1988) · European Journal of Pediatrics · doi:10.1007/bf00442624 · Cited by 22 · see citing works
Sclerosteosis: a marker of dutch ancestry?
Alves, A. F. P., Rubim, J. L. C., Cardoso, L. P., & Rabelo, M. M. (1982) · Cited by 20 · see citing works
Jones, K. A., M.Black, D., Brown, M. A., et al. (1994) · Human Molecular Genetics · doi:10.1093/hmg/3.11.1927 · Cited by 14 · see citing works
Cook, J. V., Phelps, P. D., & Chandy, J. (1989) · British Journal of Radiology · doi:10.1259/0007-1285-62-733-74 · Cited by 9 · see citing works
Pietruschka, G. (1958) · PubMed · Cited by 8 · see citing works
[Partial empty sella turcica in Van Buchem's disease].
Muiño Míguez, A., Esteban, B. M., Ramallo, V. J. G., Molina Quiñones, J., Hernández, J. A., Lafuente, J., & Albarrán, A. J. (1986) · PubMed · Cited by 6 · see citing works
[Endosteal hyperostosis with recessive transmission (Van Buchem's disease). A case report].
Bettini, R., Sessa, V., Mingardi, R., Molinari, A., Anzani, P., & Vezzetti, V. (1991) · PubMed · Cited by 6 · see citing works
[Hyperostosis corticalis generalisata (Van Buchem)].
del Campo Matías, F., de Paula, J. M. P., & Jl, C. S. (1985) · PubMed · Cited by 5 · see citing works
Flagged first, then by citations
Research works printed but not linked: 5
- Lopez AG, Pinero ML, Varo FM. Hiperostosis cortical generalizada (van Buchem). Rev Clin Esp 1985;177:293-4.
- Truswell AS. Osteopetrosis with syndactyly, a morphologic variant of Albers-Schönberg disease. J Bone Jt Surg Br 1958;40:208-18.
- Hansen HG. Sklerosteose. Handbuch Kinderheilkd 1967;6:351-5.
- Witkop CJ. Genetic diseases of the oral cavity. In: Tiecke RW, ed. Oral pathology. New York: McGraw-Hill 1965:834-43.
- Pietruscka G. Weitere Mitteilungen über die Marmorknochenkrankheit (Albers-Schönbergsche Krankheit) nebst Bemerkungen zur Differentialdiagnose. Klin Monatsbl Augenheilkd 1958;132:509-25.
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Baron, R., & Kneissel, M. (2013) · Nature Medicine · doi:10.1038/nm.3074 · Cited by 2,093 · see citing works
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Robling, A. G., Niziolek, P. J., Baldridge, L. A., Condon, K. W., Allen, M. R., Alam, I., Mantila, S. M., Gluhak-Heinrich, J., Bellido, T. M., Harris, S. E., et al. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m705092200 · Cited by 1,350 · see citing works
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Farr, J. N., Roforth, M. M., Fujita, K., Nicks, K. M., Cunningham, J. M., Atkinson, E. J., Therneau, T. M., McCready, L. K., Peterson, J. M., Drake, M. T., et al. (2015) · PLOS ONE · doi:10.1371/journal.pone.0138347 · Cited by 75 · see citing works
- Authors
- Balemans, W., Patel, N., Ebeling, M., Van Hul, E., Wuyts, W., Lacza, C., Dioszegi, M., Dikkers, F. G., Hildering, P., Willems, P. J., Verheij, J. B. G. M., Lindpaintner, K., Vickery, B., Foernzler, D., & Van Hul, W.
- Affiliations
- University of Antwerp (BE)
- Roche (United States) (US)
- F. Hoffmann-La Roche AG (CH)
- University Medical Center Groningen (NL)
- Erasmus University Rotterdam (NL)
- Venue
- Journal of Medical Genetics
- Publisher
- BMJ
- Published
- 2002-02
- Volume
- 39
- Issue
- 2
- Pages
- 91-97
- ISSN
- 0022-2593 (ISSN-L)
- 1468-6244
- PMC
- PMC1735035
- OpenAlex
- W2155377428
- Cited by
- 698
- References
- 37
- Citations by year
- 2026: 10 · 2025: 10 · 2024: 22 · 2023: 17 · 2022: 23 · 2021: 30 · 2020: 42 · 2019: 36 · 2018: 39 · 2017: 41 · 2016: 46 · 2015: 56 · 2014: 41 · 2013: 47 · 2012: 38
- FWCI
- 5.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Medical Genetics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- Fonds Wetenschappelijk Onderzoek
- Universiteit Antwerpen
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Connective tissue disorders research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Dermatological and Skeletal Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Keywords
- van Buchem disease, sclerosteosis, SOST gene, skeletal dysplasia, gene downregulation, positional cloning, autosomal recessive inheritance
- MeSH terms
- Aged, Base Sequence, Consanguinity, DNA Mutational Analysis, Female, Genetic Markers, Humans, Genetic Linkage, Male, Molecular Sequence Data, Osteochondrodysplasias, Proteins, Sequence Deletion, Bone Morphogenetic Proteins, Adaptor Proteins, Signal Transducing
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