Dyschondrosteosis1 (DCS) is an autosomal dominant2 form of mesomelic dysplasia with deformity of the forearm (Madelung deformity; ref. 3). Based on the observation of XY translocations (p22,q12; refs 4–6) in DCS patients, we tested the pseudoautosomal region in eight families with DCS and showed linkage of the DCS gene to a microsatellite DMA marker at the DXYS233 locus (Zmax=6.26 at θ=0). The short stature homeobox-containing gene7,8 (SHOX), involved in idiopathic growth retardation and possibly Turner short stature, maps to this region and was therefore regarded as a strong candidate gene in DCS. Here, we report large-scale deletions (in seven families) and a nonsense mutation (in one family) of SHOX in patients with DCS and show that Langer mesomelic dwarfism9 results from homozygous mutations at the DCS locus.
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Leri, A. & Weill, J. Une affection congénitale et symétrique du développement osseux: la dyschondrostéose. Bull. Mém. Soc. Med. Hosp. 35, 1491–1494 (1929).
Lichtenstein, J.R., Sundaram, M. & Burdge, R. Sex-influenced expression of Madelung's deformity in a family with dyschondrosteosis. J. Med. Genet. 17, 41–43 (1980).
Madelung, V. Die spontane subluxation der Hand nach Vorne. Arch. Klin. Chir. 23, 395–412 (1878).
Pfeiffer, R.A. Observations in a case of an X/Y translocation, t(X;Y)(p22;q11) in a mother and son. Cytogenet.Cell. Genet. 26, 150–157 (1980).
Castillo, S., Youlton, R. & Be, C. Dyschondrosteosis is controlled by X and Y linked loci. Cytogenet Cell. Genet. 40, 601–602 (1985).
Guichet, A. .et al. Are t(X;Y)(p22;q11) translocations in females frequently associated with Madelung deformity? Clin. Dysmorph. 6, 341–345 (1997)
Rao, E. et al. Pseudoautosomal deletions encompassing novel homeobox gene cause growth failure in idiopathic short stature and Turner syndrome. Nature Genet. 16, 54–62 (1997).
Ellison, J.W. et al. PHOG a candidate gene for involvement in the short stature of Turner syndrome. Hum. Mol. Genet. 6, 1341–1347 (1997).
Esperitu, C., Chen, H. & Wooley, P. Mesomelic dwarfism as the homozygous expression of dyschondrosteosis. Am. J. Dis. Child. 129, 375–377 (1975).
Toutain, A. et al. Dysplasie mésomélique de Reinhart-Pfeiffer ou dyschondrostéose? La distinction est-elle fondée? Ann. Pediatr. 38, 37–45 (1991).
Ballabio, A. et al. Contiguous gene syndromes due to deletions in the distal short arm of the human X chromosome. Proc. Natl. Acad. Sci. USA 86, 10001–10005 (1989)
Ogata, T. et al. Chromosomal localisation of a pseudoautosomal growth gene(s). J. Med. Genet. 29, 624–628 (1992)
Dib, C. et al. A comprehensive genetic map of the human genome based on 5264 microsatellites. Nature Genet. 380, 152–154 (1996).
Collins, A. et al. A metric map of humans: 23,500 loci in 850 bands. Proc. Natl. Acad. Sci. USA 93, 14771–14775 (1996)
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Belin, V., Cusin, V., Viot, G. et al. SHOX mutations in dyschondrosteosis (Leri-Weill syndrome) . Nat Genet 19, 67–69 (1998). https://doi.org/10.1038/ng0198-67
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