Allelic and nonallelic heterogeneity in dyschondrosteosis (Leri-Weill syndrome)

Dyschondrosteosis (DCS) is an autosomal dominant form of mesomelic dysplasia that has been recently ascribed to large-scale deletions and nonsense mutations of the SHOX gene on the pseudoautosomal region of chromosome X and Y Belin et al., 1998: Nat Genet 19:67-69; Shears et al., 1998: Nat Genet 19:70-73]. Here, we report the molecular analysis of a total of 23 DCS families including 16 previously reported pedigrees Belin et al., 1998: Nat Genet 19:67-69; Huber et al., 2001: J Med Genet 38:281-284] and 7 novel DCS families. Linkage analyses in 21 of 23 families were consistent with linkage to the pseudoautosomal region. However, in 2 of 23 families, linkage studies excluded SHOX as the disease-causing gene, suggesting that this condition is genetically heterogeneous.