PSEUDOAUTOSOMAL DELETIONS ENCOMPASSING A NOVEL HOMEOBOX GENE CAUSE GROWTH FAILURE IN IDIOPATHIC SHORT STATURE AND TURNER-SYNDROME

Growth retardation resulting in short stature is a major concern for p arents and due to its great variety of causes, a complex diagnostic ch allenge for clinicians. A major locus involved in linear growth has be en implicated within the pseudoautosomal region (PAR1) of the human se x chromosomes. We have determined an interval of 170 kb of DNA within PAR1 which was deleted in 36 individuals with short stature and differ ent rearrangements on Xp22 or Yp11.3, This deletion was not detected i n any of the relatives with normal stature or in a further 30 individu als with rearrangements on Xp22 or Yp11.3 with normal height, We have isolated a homeobox-containing gene (SHOX) from this region, which has at least two alternatively spliced forms, encoding proteins with diff erent patterns of expression. We also identified one functionally sign ificant SHOX mutation by screening 91 individuals with idiopathic shor t stature. Our data suggest an involvement of SHOX in idiopathic growt h retardation and in the short stature phenotype of Turner syndrome pa tients.