SHOX mutations in dyschondrosteosis (Leri-Weill syndrome).
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.
Belin
V
V
Département de Génétique et Unité de Recherches sur les Handicaps Génétiques de l'Enfant INSERM U393, Hôpital des Enfants Malades, Paris, France.
Cusin
V
V
Viot
G
G
Girlich
D
D
Toutain
A
A
Moncla
A
A
Vekemans
M
M
Le Merrer
M
M
Munnich
A
A
Cormier-Daire
V
V
D005260:Female; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010009:Osteochondrodysplasias / Q000235:genetics*; D010375:Pedigree; D000074122:Short Stature Homeobox Protein; D014178:Translocation, Genetic; D014960:X Chromosome; D014998:Y Chromosome
D018398:Homeodomain Proteins; C106071:SHOX protein, human; D000074122:Short Stature Homeobox Protein