SHOX gene mutations and deletions in dyschondrosteosis or Leri-Weill syndrome

Dyschondrosteosis is an autosomal dominant form of mesomelic dysplasia that is often combined with a deformity of the forearms called Madelung deformi ty. Based on the observation of X-Y translocations (p22,q12) in patients wi th dyschondrosteosis, the authors rested the pseudoautosomal region in eigh t affected families and showed linkage of the dyschondrosteosis gene to a m icrosatellite DNA marker at the DXYS233 locus (Z(max) = 6.26 at theta = 0). Since the short stature homeobox-containing gene (SHOX) involved in idiopa thic growth retardation and possibly Turner syndrome maps to this region, S HOX was regarded as a strong candidate gene for dyschondrosteosis. This art icle reports the detection of large-scale SHOX deletions in seven of the ei ght families and a nonsense mutation of SHOX in the remaining family affect ed with dyschondrosteosis. Additional evidence suggests that Langer mesomel ic dwarfism results from homozygous mutations at the genetic locus responsi ble for dyschondrosteosis.