SHOX haploinsufficiency and overdosage: impact of gonadal function status

Citation
T. Ogata et al., SHOX haploinsufficiency and overdosage: impact of gonadal function status, J MED GENET, 38(1), 2001, pp. 1-6
Citations number
38
Language
INGLESE
art.tipo
Review
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Molecular Biology & Genetics
Journal title
JOURNAL OF MEDICAL GENETICS
ISSN journal
0022-2593 → ACNP
Volume
38
Issue
1
Year of publication
2001
Pages
1 - 6
Database
ISI
SICI code
0022-2593(200101)38:1<1:SHAOIO>2.0.ZU;2-Y
Abstract
Since its discovery in 1997, knowledge about the SHOX gene has rapidly incr eased. In this review, we summarise clinical features and diagnostic and th erapeutic implications in SHOX haploinsufficiency and overdosage. SHOX hapl oinsufficiency usually results in mesomelic short stature and Turner skelet al features, including Madelung deformity with puberty, in subjects with no rmal gonadal function. Thus, identification of early or mild signs of Madel ung deformity is pivotal for the diagnosis, and gonadal suppression therapy may serve to mitigate the clinical features. By contrast, SHOX overdosage usually leads to long limbs and tall stature resulting from continued growt h into the late teens in subjects with gonadal dysgenesis. Thus, the combin ation of tall stature and poor pubertal development is the key to diagnosis , and oestrogen therapy can help the prevention of unfavourably tall statur e as well as the induction of sexual development. These findings, in conjun ction with skeletal assessment in Turner syndrome and expression analysis d uring human embryogenesis, imply that SHOX functions as a repressor for gro wth plate fusion and skeletal maturation in the distal limbs and, thus, cou nteracts the skeletal maturing effects of oestrogens.