Heterozygous mutations in natriuretic peptide receptor-B (NPR2) are associated with short stature
Heterozygous mutations in natriuretic peptide receptor-B (NPR2) are associated with short stature
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DOI：
10.1210/jc.2005-1949
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发表时间：
2006-04-01
影响因子：
5.8
通讯作者：
Warman, ML
中科院分区：
文献类型：
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作者：
Olney, RC;Bükülmez, H;Warman, ML
背景：C 型钠尿肽 (CNP) 是骨骼生长的重要调节因子。影响 CNP 受体利钠肽受体 B（基因 NPR2）的功能丧失突变会导致常染色体隐性遗传性骨骼发育不良、顶体发育不良、Maroteaux 型 (AMDM)。 NPR2 突变杂合子携带者的表型尚不清楚。目的：本研究的目的是确定 NPR2 突变杂合子携带者的表型特征。设计和背景：这是一项来自普通社区的病例对照研究。受试者：研究了一个家庭的 39 名成员，其中一名成员患有 AMDM。干预：这是一项观察性研究。主要结果测量：主要测量是身高，假设携带者与非携带者相比身材矮小。结果：16 个家庭成员是 NPR2 突变携带者。这些携带者的身高 z 得分为 -1.8 +/- 1.1（平均值 +/- SD），显着低于 23 名非携带者家庭成员（-0.4 +/- 0.8，P < 0.0005）和一般人群（P < 0.0005）。然而，携带者和非携带者之间的身体比例没有差异。患有 AMDM 的先证者具有较低的 IGF-I 水平和 GH 抵抗的证据，以及非常高的血浆 CNP 及其氨基末端前肽水平。这些肽的水平在杂合子携带者中是正常的。结论：我们已经证明，NPR2 的杂合子突变与身材矮小有关。假设每 700 人中就有 1 人在不知情的情况下携带 NPR2 突变，我们的数据表明，大约每 30 名特发性矮身材个体中就有 1 人是 NPR2 突变携带者。
Context: C-type natriuretic peptide (CNP) is an important regulator of skeletal growth. Loss-of-function mutations affecting the CNP receptor natriuretic peptide receptor-B (gene NPR2) cause the autosomal recessive skeletal dysplasia, acromesomelic dysplasia, Maroteaux type (AMDM). The phenotype of heterozygous carriers of NPR2 mutations is less clear.Objective: The objective of the study was to determine the phenotypic features of heterozygous carriers of NPR2 mutations.Design and Setting: This was a case-control study from the general community.Subjects: Thirty-nine members of a family in which one member has AMDM were studied.Intervention: This was an observational study.Main Outcome Measure: The primary measure was stature, with the hypothesis that carriers have reduced stature compared with noncarriers.Results: Sixteen family members were NPR2 mutation carriers. Height z-scores of these carriers were -1.8 +/- 1.1 (mean +/- SD), which was significantly less than the 23 noncarrier family members (-0.4 +/- 0.8, P < 0.0005) and the general population (P < 0.0005). However, there was no difference in body proportion between carriers and noncarriers. The proband with AMDM had low IGF-I levels and evidence of GH resistance, as well as very high plasma levels of CNP and its amino-terminal propeptide. Levels of these peptides were normal in the heterozygous carriers.Conclusions: We have shown that heterozygous mutations in NPR2 are associated with short stature. Assuming one in 700 people unknowingly carry an NPR2 mutation, our data suggest that approximately one in 30 individuals with idiopathic short stature are carriers of NPR2 mutations.