• Leri-Weill dyschondrosteosis
• SHOX point mutations

SHOX (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.¹ The finding of a mutation generating a premature stop codon in exon 5 of SHOX, cosegregating with idiopathic short stature (ISS), provided evidence for the involvement of this gene in growth retardation, including the short stature of Turner syndrome.¹ 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.⁴

Some 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.