Phenotypes Associated with SHOX Deficiency.
Phenotypes Associated with SHOX Deficiency.
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DOI：
10.1210/jcem.86.12.8125
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发表时间：
2001-12
期刊：
影响因子：
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通讯作者：
Judith L. Ross;Charles I. Scott;Pia Marttila;Karen Kowal;Andrea Nass;Peter Papenhausen;Jack Abboudi;Lee Osterman;Harvey Kushner;Peter R. Carter;Marybeth Ezaki;Frederick F.B. Elder;Fanglin Wei;Huaqun Chen;A. Zinn
中科院分区：
文献类型：
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作者：
Judith L. Ross;Charles I. Scott;Pia Marttila;Karen Kowal;Andrea Nass;Peter Papenhausen;Jack Abboudi;Lee Osterman;Harvey Kushner;Peter R. Carter;Marybeth Ezaki;Frederick F.B. Elder;Fanglin Wei;Huaqun Chen;A. Zinn
Leri-Weill软骨发育不良（LWD）（MIM 127300）是一种显性遗传性骨骼发育不良，其表型特征为Madelung腕畸形、间肢畸形和身材矮小。LWD现在可以通过SHOX（含身材矮小同源框）基因的单倍不足在遗传学上定义。我们研究了21个LWD家庭（43个受影响的LWD受试者，包括32名女性和11名男性，年龄3-56岁）与确认SHOX异常。我们研究了SHOX突变、身高缺陷和Madelung畸形之间的关系，以确定SHOX单倍不足对LWD和Turner综合征（TS）表型的贡献。此外，我们还研究了年龄、性别和女性青春期（雌激素）对LWD表型的影响。17个家系（81%）的患者存在SHOX基因缺失，4个家系（19%）存在点突变。在LWD受试者中，身高不足范围为-4.6至+0.6 SD（平均值+/- SD = -2.2 +/- 1.0）。年龄、性别、青春期状态或SHOX突变的父母来源对身高Z评分没有统计学显著影响。LWD的身高不足约为TS的三分之二。马德隆畸形存在于74%的LWD儿童和成人，女性比男性更频繁和严重。马德隆畸形的患病率在LWD人群中高于TS人群。两个人群中，背角增加、高弓腭和脊柱侧凸的患病率相似。总之，SHOX基因缺失或突变是我们所有LWD病例的原因。SHOX单倍不足占大部分，但不是全部，TS的高度赤字。LWD表型显示出一些与性别和年龄相关的差异。
Leri-Weill dyschondrosteosis (LWD) (MIM 127300) is a dominantly inherited skeletal dysplasia characterized phenotypically by Madelung wrist deformity, mesomelia, and short stature. LWD can now be defined genetically by haploinsufficiency of the SHOX (short stature homeobox-containing) gene. We have studied 21 LWD families (43 affected LWD subjects, including 32 females and 11 males, ages 3-56 yr) with confirmed SHOX abnormalities. We investigated the relationship between SHOX mutations, height deficit, and Madelung deformity to determine the contribution of SHOX haploinsufficiency to the LWD and Turner syndrome (TS) phenotypes. Also, we examined the effects of age, gender, and female puberty (estrogen) on the LWD phenotype. SHOX deletions were present in affected individuals from 17 families (81%), and point mutations were detected in 4 families (19%). In the LWD subjects, height deficits ranged from -4.6 to +0.6 SD (mean +/- SD = -2.2 +/- 1.0). There were no statistically significant effects of age, gender, pubertal status, or parental origin of SHOX mutations on height z-score. The height deficit in LWD is approximately two thirds that of TS. Madelung deformity was present in 74% of LWD children and adults and was more frequent and severe in females than males. The prevalence of the Madelung deformity was higher in the LWD vs. a TS population. The prevalence of increased carrying angle, high arched palate, and scoliosis was similar in the two populations. In conclusion, SHOX deletions or mutations accounted for all of our LWD cases. SHOX haploinsufficiency accounts for most, but not all, of the TS height deficit. The LWD phenotype shows some gender- and age-related differences.