基因的杂合突变在利钠肽receptor-B (NPR2)引起的身材矮小患者最初分为特发性身材矮小。
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Vasques GA,天野之弥N, Docko AJ, Funari MF,组织EP, Nishi我,这些IJ,长谷川T,豪尔赫AA
基因的杂合突变在利钠肽receptor-B (NPR2)引起的身材矮小患者最初分为特发性身材矮小。
中国性金属底座。2013年10月,98 (10):E1636-44。doi: 10.1210 / jc.2013 - 2142。Epub 2013年9月3。
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24001744 (在PubMed]
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背景:基于地位acromesomelic发育不良患者的亲属中观察到,Maroteaux类型,利钠肽B受体基因的纯合子突变(NPR2),有人建议,在这个基因的杂合突变可能负责增长障碍中观察到一些孩子与特发性身材矮小(ISS)。目的:这项研究的目的是调查的存在NPR2突变组患者的空间站。患者和方法:NPR2编码区直接测序在47个独立的空间站的患者。NPR2的功能后果产生的变化建立了用体外细胞化验。结果:三个小说杂合的NPR2突变被发现:c。226 t > C (p.Ser76Pro), C。788 g > C (p.Arg263Pro), C。2455 c > T (p.Arg819Cys)。这些等位变异没有发现在我们的控制或1000基因组数据库。在硅片分析表明,三个错义突变可能是有害的。他们都是选择的体外功能评估。细胞转染与三个突变体未能产生环磷鸟苷与c型利钠肽治疗后。 Cells cotransfected with mutant and wild-type-NPR-B (1:1) showed a significant decrease in cGMP levels after C-type natriuretic peptide stimulation in comparison with cells cotrasnfected with empty vector and wild type, suggesting a dominant-negative effect. These three mutations segregated with short stature phenotype in an autosomal dominant pattern (height SD score ranged from -4.5 to -1.7). One of these patients and two relatives have disproportionate short stature, whereas in another patient a nonspecific skeletal abnormality was observed. All three of these patients were treated with recombinant human GH (33-50 mug/kg . d) without significant height SD score change during therapy. CONCLUSIONS: We identified heterozygous NPR2 mutations in 6% of patients initially classified as ISS. Affected patients have mild and variable degrees of short stature without a distinct phenotype. Heterozygous mutations in NPR2 could be an important cause of nonsyndromic familial short stature.