SHOX point mutations and deletions in Leri-Weill dyschondrosteosis

HOX (Short HOmeoboX containing gene) (OMIM 312865) is the single gene found in the "short stature critical region", a 170 kb DNA segment of the pseudoautosomal (PAR1) region identified through genotype/ phenotype correlations in X/Y abnormalities. At the heterozygous level, large deletions or point mutations of the SHOX gene have been found in families affected by Leri-Weill dyschondrosteosis (LWD, OMIM 127300), a dominantly inherited skeletal dysplasia with disproportionate short stature owing to mesomelic shortening of the forearm and lower leg and Madelung deformity of the arm. 2 3 In addition, the biallelic inactivation of the SHOX gene was shown in fetuses with Langer-type mesomelic dysplasia (OMIM 249700), 2 3 a recessive form of dwarfism which was confirmed as the homozygous counterpart of LWD, as previously proposed on a clinical genetic basis. ome authors reported mutations in all the LWD cases studied, 3 5 whereas others found SHOX mutations in about 60% of the cases. 6 7 The same proportion of SHOX gene mutations are reported in the present study based on the analysis of a large group of Italian LWD families.