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SHOX mutations in dyschondrosteosis (Leri-Weill syndrome)


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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Correspondence to Arnold Munnich.

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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).

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