Characterization of SHOX Deletions in Léri-Weill Dyschondrosteosis (LWD) Reveals Genetic Heterogeneity and No Recombination Hotspots

In the July 2005 and March 2006 issues of the Journal, Schneider et al.1 and Zinn et al.,2 respectively, reported mapping studies of SHOX (MIM 312865) deletions in patients with Leri-Weill dyschondrosteosis (LWD [MIM 127300]). In their study, Schneider et al.1 reported that the majority (73%) of patients with LWD who had SHOX deletions shared a 3? deletion breakpoint hotspot located downstream of SHOX. Zinn et al.2 identified a different 3? breakpoint hotspot located several hundred kilobases farther downstream in 86% of Hispanic patients, whereas the recombination hotspot described by Schneider et al.1 was not observed. We characterized the SHOX deletion limits in a cohort of 48 European patients with LWD (n=47) and Langer mesomelic dysplasia (LMD [MIM 249700]) (n=1). SHOX deletions were originally detected by multiplex ligation probe amplification (MLPA) (MRC Holland) or microsatellite analysis (DXYS10092, DXYS201, DYS290, DXYS10093, DXYS233, and DXYS234) and subsequently were finely mapped using a dense panel of microsatellites and SNPs.3 Four newly identified microsatellites (Tandem Repeat Finder), located 133, 54, 31, and 19 kb 5? of SHOX (table 1), and 59 SNPs, 12 of which were previously unreported (table 2), were analyzed.