Short stature homeobox-containing gene duplication on the der(X) chromosome in a female with 45,X/46,X, der(X), gonadal dysgenesis, and tall stature

We report on a Japanese female with 45,X[40]/46,X, der(X)[GO], primary amen orrhea, and tall stature. She was confirmed to have complete gonadal dysgen esis at 19 yr of age and was placed on hormone replacement therapy. Growth assessment revealed that she had a low normal height until her early teens, but continued to grow with a nearly constant height velocity in her late t eens, attaining a final height of 172 cm (+2.9 so), which surpassed her tar get height range. Fluorescence in situ hybridization analysis for 10 loci/r egions on the X-chromosome together with the whole X-chromosome and the Xp- specific and Xq-specific paintings showed that the der(X) chromosome was as sociated with duplication of roughly distal half of Xp, including SHOX (sho rt stature homeobox-containing gene), and deletion of most of Xq. Microsate llite analysis for eight loci at Xp22 and nine loci at Xq26-28 indicated th at the normal X-chromosome was of maternal origin, and the der(X) chromosom e was of paternal origin. The results, in conjunction with the adult height data in 47,XXX, 46,XX gon adal dysgenesis, 47,XXY, 46,XY gonadal dysgenesis, and 46,X, idic(Xq-), sug gest that the tall stature of this female is caused by the combined effects of SHOX duplication on the der(X) chromosome and gonadal estrogen deficien cy. Furthermore, the similarity in the growth pattern between this female a nd patients with estrogen resistance or aromatase deficiency implies that t he association of an extra copy of SHOX with gonadal estrogen deficiency ma y represent the further clinical entity for tall stature resulting from con tinued growth in late teens or into adulthood.