SHOX mutations in dyschondrosteosis (Leri-Weill syndrome)

Abstract

Dyschondrosteosis (DCS) is an autosomal dominant 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 DNA marker at the DXYS233 locus (Zmax=6.26 at theta=0). The short stature homeobox-containing gene (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 dwarfism results from homozygous mutations at the DCS locus.

A reinvestigation of non-disjunction resulting in 47, XXY males of paternal origin

“…The identification of PAR 1 microdeletions in patients with LWD 16,17 suggests a possible mechanism to explain some cases of paternal sex chromosome non-disjunction. However, we could find no evidence for the presence of any deletions as large as those reported in LWD, although the presence of much smaller deletions could not be excluded.…”

“…Submicroscopic deletions encompassing the SHOX gene within PAR 1 have recently been identified as the causative mutation in 12 families with Leri-Weill dyschondrosteosis (LWD), a dominantly inherited skeletal dysplasia. 16,17 Such deletions would reduce the extent of X/Y homology and could have a similar effect on pairing or recombination. To test the hypothesis that PAR 1 deletions would increase the risk of sex chromosome non-disjunction, we have screened our series of paternal 47, XXYs for PAR 1 microdeletions using a total of seven microsatellites across the region.…”

Linkage disequilibrium in inbred North African families allows fine genetic and physical mapping of triple A syndrome

“…Electrophoresis was performed at 70 W for 1-3 h. Gels were blotted on to nylon membranes (Appligene, Illkirch, France), labelled by chemiluminescence according to the manufacturer's instructions (ECL, Amersham, Buckinghamshire, UK), and exposed to X-ray film for 10 min. 11 …”

PAR1 deletions downstream ofSHOX are the most frequent defect in a Spanish cohort of Léri-Weill dyschondrosteosis (LWD) probands

“…SHOX (MIM# 312865) mutations or deletions have been reported in LWD (Belin et al, 1998;Shears et al, 1998). We recently identified the presence of a new class of pseudoautosomal region 1 (PAR1) deletion in LWD that do not include SHOX.…”