SHOX Haploinsufficiency as a Cause of Syndromic and Nonsyndromic Short Stature

• Published in: Molecular syndromology Vol. 7; no. 1; pp. 3 - 11
• Main Authors: Fukami, Maki, Seki, Atsuhito, Ogata, Tsutomu
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.04.2016
• Subjects: Review; Review Article; Léri-Weill syndrome; Skeletal deformity; Pseudoautosomal region; Short stature; Bone; Mutation; Turner syndrome
• ISSN: 1661-8769; 1661-8777
• DOI: 10.1159/000444596

SHOX in the short arm pseudoautosomal region (PAR1) of sex chromosomes is one of the major growth genes in humans. SHOX haploinsufficiency results in idiopathic short stature and Léri-Weill dyschondrosteosis and is associated with the short stature of patients with Turner syndrome. The SHOX protein likely controls chondrocyte apoptosis by regulating multiple target genes including BNP, Fgfr3, Agc1, and Ctgf. SHOX haploinsufficiency frequently results from deletions and duplications in PAR1 involving SHOX exons and/or the cis-acting enhancers, while exonic point mutations account for a small percentage of cases. The clinical severity of SHOX haploinsufficiency reflects hormonal conditions rather than mutation types. Growth hormone treatment seems to be beneficial for cases with SHOX haploinsufficiency, although the long-term outcomes of this therapy require confirmation. Future challenges in SHOX research include elucidating its precise function in the developing limbs, identifying additional cis-acting enhancers, and determining optimal therapeutic strategies for patients.