Trisomy of the short stature homeobox-containing gene (SHOX), resulting from a duplication-deletion of the X chromosome

Clin Endocrinol (Oxf). 2002 May;56(5):671-5. doi: 10.1046/j.1365-2265.2002.01504.x.

Abstract

The Turner syndrome (TS) is a complex disorder associated with almost invariant short stature and gonadal dysgenesis, as well as a variety of other major organ malformations. Recently, a homeobox-containing gene entitled short-stature homeobox-containing gene (SHOX), was isolated from a minimal short stature gene interval from the pseudoautosomal region of Xp (and Yp). Together with the demonstrable escape of SHOX from X-inactivation, this suggested SHOX to be a strong candidate gene for the short stature component of TS, and as SHOX haploinsufficiency appears to be the molecular basis of a mesomelic short statured skeletal dysplasia (Leri-Weill syndrome), this suggested that SHOX protein expression levels may confer a dosage effect on human stature. However, in this communication we report a normal statured female with gonadal dysgenesis, due to the inheritance of a recombinant duplication-deletion X-chromosome. The karyotype of the proband was 46,X,rec(X)dup(Xp)inv(X)(p11.22q21.2)mat and fluorescent in situ hybridization of her metaphases with a SHOX cosmid confirmed the proband to be trisomic for SHOX. This communication suggests the relationship between levels of SHOX expression and human stature to be more complex than envisaged previously. The presence of normal stature in our patient rather than tall stature is likely to represent the natural variation seen in patients with transcription factor disorders.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Body Height / genetics*
  • Dosage Compensation, Genetic
  • Estrogen Replacement Therapy
  • Female
  • Gonadal Dysgenesis, 46,XX / drug therapy
  • Gonadal Dysgenesis, 46,XX / genetics*
  • Homeodomain Proteins / genetics*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Short Stature Homeobox Protein
  • Trisomy*
  • X Chromosome / genetics*

Substances

  • Homeodomain Proteins
  • SHOX protein, human
  • Short Stature Homeobox Protein