Clinical significance of the parental origin of the X chromosome in Turner syndrome
Clinical significance of the parental origin of the X chromosome in Turner syndrome
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DOI：
10.1210/jc.2006-0158
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发表时间：
2007-03-01
影响因子：
5.8
通讯作者：
Hochberg, Ze'ev
中科院分区：
文献类型：
--
作者：
Sagi, Liora;Zuckerman-Levin, Nehama;Hochberg, Ze'ev
研究背景：特纳综合征（TS）的表型是可变的，即使在假定为非镶嵌核型的患者中也是如此。以前的工作表明，有X连锁的父母的原产地的影响上的phenotype.Hypothesis：TS表型是受父母的起源错过的X chromosome.Design：这是一个多中心的前瞻性研究TS患者和他们的父母，确定父母的X染色体的起源，并表征临床phenotype.Patients和方法：83 TS患者和他们的父母进行了研究。入选标准为核型为45，X或46 Xi（Xq）的TS。X染色体DMD 49、DYSII、DXS 1283和雄激素受体基因上的4个高度多态性微卫星标记以及3个Y染色体标记SRY、DYZ 1和DYZ 3。该研究确定了X染色体的父母起源与TS的独特表型性状之间的相关性，包括先天性畸形、人体测量和生长模式、骨骼缺陷、内分泌性状、教育、结果：83%的45，X保留了其母体X（X-m），而64%的46 Xi（Xq）保留了其父体X（X-p，P < 0.001）。肾畸形仅见于Xm患者（P = 0.030）。Xm组总胆固醇和低密度脂蛋白胆固醇较低（P < 0.003），体重指数SD评分较高（P = 0.030），GH治疗后未维持。对GH治疗的反应相当。眼部异常更常见于父亲的X组（P = 0.017），谁也有较高的学术成就。结论：父母的X染色体的短臂失踪的起源有超重，肾脏，眼睛和脂质的影响，这表明一个尚未确定的X染色体基因印迹的潜在影响。
Context: The phenotype in Turner syndrome (TS) is variable, even in patients with a supposedly nonmosaic karyotype. Previous work suggested that there were X-linked parent-of-origin effects on the phenotype.Hypothesis: The TS phenotype is influenced by the parental origin of the missed X chromosome.Design: This was a multicenter prospective study of TS patients and both their parents, determining parental origin of the X-chromosome, and characterizing the clinical phenotype.Patients and Methods: Eighty-three TS patients and their parents were studied. Inclusion criteria were TS with karyotype 45, X or 46Xi(Xq). Four highly polymorphic microsatellite markers on the X-chromosome DMD49, DYSII, DXS1283, and the androgen receptor gene and three Y chromosome markers, SRY, DYZ1, and DYZ3.Outcome Measures: The study determined the correlation between the parental origin of the X chromosome and the unique phenotypic traits of TS including congenital malformations, anthropometry and growth pattern, skeletal defects, endocrine traits, education, and vocation.Results: Eighty-three percent of 45, X retained their maternal X (X-m), whereas 64% 46Xi( Xq) retained their paternal X (X-p, P < 0.001). Kidney malformations were exclusively found in Xm patients (P = 0.030). The Xm group had lower total and low-density lipoprotein cholesterol (P < 0.003), and higher body mass index SD score (P = 0.030) that was not maintained after GH treatment. Response to GH therapy was comparable. Ocular abnormalities were more common in the paternal X group (P = 0.017), who also had higher academic achievement.Conclusions: The parental origin of the missing short arm of the X chromosome has an impact on overweight, kidney, eye, and lipids, which suggests a potential effect of an as-yet-undetermined X chromosome gene imprinting.