University Children's Hospital, Pediatric Endocrinology and Diabetology, Tübingen, Germany. gerhard.binder @ med.uni-tuebingen.de
Horm Res Paediatr. 2011 Feb;75(2):81-9. doi: 10.1159/000324105. Epub 2011 Feb 4.
SHOX deficiency is a frequent cause of short stature. The short stature homeobox-containing gene resides in the telomeric PAR1 region on the short arm of both sex chromosomes and escapes X inactivation. For this review, abstracts of 207 publications presented by PubMed for the search term 'SHOX' were screened. Heterozygote SHOX mutations (80% deletions) were detected in 2-15% of individuals with formerly idiopathic short stature, in 50-90% of individuals with Leri-Weill dyschondrosteosis, and in almost 100% of girls with Turner syndrome. Mutational analysis is primarily performed by MLPA analysis followed by gene sequencing if necessary. SHOX is a nuclear protein that binds to DNA and acts as a transcriptional activator. Orthologs are present in many vertebrates but not in rodents. Gene expression starting as early as 33 days postconception in humans is predominant in the mid portion of the buds and in the first and second pharyngeal arches. In the growth plate, hypertrophic chondrocytes express SHOX where it seems to have antiproliferative potency. The penetrance of SHOX deficiency is high, but its clinical expression is very variable becoming more pronounced with age and being more severe in females. Growth failure starts early during the first years of life and the height deficit present at preschool age seems not to deteriorate further. The mean adult height is -2.2 SDS. Auxological analysis of the body proportions (mesomelia), the presence of minor abnormalities, and the search for subtle radiographic signs are important keys to the diagnosis which has to be confirmed by genetic analysis. The growth-promoting effect of GH therapy approved for individuals with SHOX mutations seems to be equal to the effect seen in Turner syndrome.
SHOX 缺失是身材矮小的常见原因。短指同源盒基因位于性染色体短臂的端粒 PAR1 区域，逃避 X 染色体失活。为了进行本次综述，对 PubMed 检索词“SHOX”下的 207 篇文献摘要进行了筛选。在以前的特发性身材矮小患者中，2-15%存在杂合 SHOX 突变（80%缺失），在 Leri-Weill 软骨发育不全患者中，50-90%存在杂合 SHOX 突变，在几乎所有特纳综合征女孩中都存在杂合 SHOX 突变。突变分析主要通过 MLPA 分析进行，如果需要，则进行基因测序。SHOX 是一种核蛋白，可与 DNA 结合并作为转录激活因子发挥作用。在许多脊椎动物中都存在同源物，但在啮齿动物中不存在。在人类中，受精卵后 33 天就开始表达 SHOX，主要在芽的中部和第一、二咽弓表达。在生长板中，肥大软骨细胞表达 SHOX，其似乎具有抗增殖作用。SHOX 缺失的外显率很高，但临床表达非常多样，随着年龄的增长而变得更加明显，在女性中更为严重。生长障碍在生命的最初几年就开始出现，学龄前的身高缺陷似乎不会进一步恶化。成年平均身高为-2.2 SDS。对身体比例（中间肢体过长）的体格分析、微小异常的存在以及对细微放射学征象的寻找是诊断的重要关键，诊断必须通过遗传分析来确认。批准用于 SHOX 突变个体的 GH 治疗的促生长作用似乎与特纳综合征中观察到的作用相当。
