Jorge Alexander A L, Nishi Mirian Y, Funari Mariana F A, Souza Silvia C, Arnhold Ivo J P, Mendonça Berenice B
Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM/42, Faculdade de Medicina, Universidade de São Paulo, SP, Brazil.
Arq Bras Endocrinol Metabol. 2008 Jul;52(5):765-73. doi: 10.1590/s0004-27302008000500008.
Studies involving patients with short stature and partial deletion of sex chromosomes identified SHOX gene in the pseudoautosomal region of the X and Y chromosomes. SHOX haploinsufficiency is an important cause of short stature in a diversity of clinical conditions. It explains 2/3 of short stature observed in Turner syndrome (TS) patients. Heterozygous mutations in SHOX are observed in 77% of patients with Leri-Weill dyschondrosteosis, a common dominant inherited skeletal dysplasia and in 3% of children with idiopathic short stature, indicating that SHOX defects are the most frequent monogenetic cause of short stature. The sitting height/height ratio (SH/H) standard deviation score is a simple way to assess body proportions and together with a careful exam of other family members, effectively selected a group of patients that presented a high frequency of SHOX mutations. Growth hormone treatment of short stature due to TS is well established and considering the common etiology of short stature in patients with isolated defects of SHOX gene, this treatment is also proposed for these patients. Here, we review clinical, molecular and therapeutic aspects of SHOX haploinsufficiency.
对身材矮小且性染色体部分缺失患者的研究在X和Y染色体的假常染色体区域鉴定出了SHOX基因。SHOX单倍剂量不足是多种临床情况下身材矮小的重要原因。它解释了特纳综合征（TS）患者中观察到的2/3的身材矮小情况。在常见的显性遗传性骨骼发育不良——勒里-韦伊软骨发育不全症患者中，77%观察到SHOX杂合突变，在特发性身材矮小儿童中，3%观察到SHOX杂合突变，这表明SHOX缺陷是身材矮小最常见的单基因病因。坐高/身高比值（SH/H）标准差评分是评估身体比例的一种简单方法，结合对其他家庭成员的仔细检查，能有效筛选出一组SHOX突变频率较高的患者。因TS导致的身材矮小采用生长激素治疗已得到充分确立，考虑到SHOX基因孤立缺陷患者身材矮小的常见病因，也建议对这些患者采用这种治疗方法。在此，我们综述SHOX单倍剂量不足的临床、分子和治疗方面的情况。
