胰岛素样生长因子1受体
基因组印记
生物
内分泌学
印记(心理学)
表型
内科学
等位基因
受体
宫内生长受限
突变
生长因子
遗传学
基因
医学
基因表达
怀孕
胎儿
DNA甲基化
作者
Denise Rockstroh,Heike Pfäffle,Diana Le Duc,Franziska Rößler,Franziska Schlensog‐Schuster,John T. Heiker,Jürgen Kratzsch,Wieland Kieß,Johannes R. Lemke,Rami Abou Jamra,Roland Pfäffle
出处
期刊:European journal of endocrinology
[Bioscientifica]
日期:2019-01-01
卷期号:180 (1): K1-K13
被引量:16
摘要
Objective The IGF/IGF1R axis is involved in the regulation of human growth. Both IGF1 and IGF2 can bind to the IGF1R in order to promote growth via the downstream PI3K/AKT pathway. Pathogenic mutations in IGF1 and IGF1R determine intrauterine growth restriction and affect postnatal body growth. However, to date, there are only few reports of pathogenic IGF2 mutations causing severe prenatal, as well as postnatal growth retardation. Results Here we describe a de novo c.195delC IGF2 variant (NM_000612, p.(Ile66Ser fs *93)) in a 4-year-old patient with severe pre- and post-natal growth retardation in combination with dystrophy, facial dimorphism, finger deformities, as well as a patent ductus. Cloning and sequencing of a long-range PCR product harboring the deletion and a SNP informative site chr11:2153634 (rs680, NC_000011.9:g.2153634T>C) demonstrated that the variant resided on the paternal allele. This finding is consistent with the known maternal imprinting of IGF2 . 3D protein structure prediction and overexpression studies demonstrated that the p.(Ile66Ser fs *93) IGF2 gene variation resulted in an altered protein structure that impaired ligand/receptor binding and thus prevents IGF1R activation. Conclusion The severity of the phenotype in combination with the dominant mode of transmission provides further evidence for the involvement of IGF2 in growth disorders.
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