SHOX gene mutations and deletions in dyschondrosteosis or Leri-Weill syndrome.
Dyschondrosteosis is an autosomal dominant form of mesomelic dysplasia that is often combined with a deformity of the forearms called Madelung deformity. Based on the observation of X-Y translocations (p22,q12) in patients with dyschondrosteosis, the authors tested the pseudoautosomal region in eight affected families and showed linkage of the dyschondrosteosis gene to a microsatellite DNA marker at the DXYS233 locus (Zmax = 6.26 at theta = 0). Since the short stature homeobox-containing gene (SHOX) involved in idiopathic growth retardation and possibly Turner syndrome maps to this region, SHOX was regarded as a strong candidate gene for dyschondrosteosis. This article reports the detection of large-scale SHOX deletions in seven of the eight families and a nonsense mutation of SHOX in the remaining family affected with dyschondrosteosis. Additional evidence suggests that Langer mesomelic dwarfism results from homozygous mutations at the genetic locus responsible for dyschondrosteosis.
Cormier-Daire
V
V
Département de Génétique, INSERM U 393, Hôpital des Enfants Malades, Paris, France.
Belin
V
V
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
D001847:Bone Diseases / Q000235:genetics*; D002648:Child; D002872:Chromosome Deletion; D004392:Dwarfism / Q000235:genetics; D005542:Forearm / Q000002:abnormalities*; D008040:Genetic Linkage; D006130:Growth Disorders / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D018895:Microsatellite Repeats; D009154:Mutation; D010375:Pedigree; D000074122:Short Stature Homeobox Protein; D013577:Syndrome
D018398:Homeodomain Proteins; C106071:SHOX protein, human; D000074122:Short Stature Homeobox Protein