FGFR3 gene mutation plus GRB10 gene duplication in a patient with achondroplasia plus growth delay with prenatal onset.

Achondroplasia is a well-defined and common bone dysplasia. Genotype- and phenotype-level correlations have been found between the clinical symptoms of achondroplasia and achondroplasia-specific FGFR3 mutations. A 2-year-old boy with clinical features consistent with achondroplasia and Silver-Russell syndrome-like symptoms was found to carry a mutation in the fibroblast growth factor receptor-3 (FGFR3) gene at c.1138G > A (p.Gly380Arg) and a de novo 574 kb duplication at chromosome 7p12.1 that involved the entire growth-factor receptor bound protein 10 (GRB10) gene. Using quantitative real-time PCR analysis, GRB10 was over-expressed, and, using enzyme-linked immunosorbent assays for IGF1 and IGF-binding protein-3 (IGFBP3), we found that IGF1 and IGFBP3 were low-expressed in this patient. We demonstrate that a combination of uncommon, rare and exceptional molecular defects related to the molecular bases of particular birth defects can be analyzed and diagnosed to potentially explain the observed variability in the combination of molecular defects. The online version of this article (doi:10.1186/s13023-016-0465-4) contains supplementary material, which is available to authorized users.

软骨发育不全是一种明确且常见的骨发育不良。在软骨发育不全的临床症状与软骨发育不全特异性的成纤维细胞生长因子受体3（FGFR3）突变之间，已发现基因型和表型层面的相关性。 一名具有与软骨发育不全相符的临床特征以及类似西尔弗 - 拉塞尔综合征症状的2岁男孩，被发现其成纤维细胞生长因子受体 - 3（FGFR3）基因在c.1138G＞A（p.Gly380Arg）处存在突变，并且在染色体7p12.1处有一个新生的574kb重复，该重复涉及整个生长因子受体结合蛋白10（GRB10）基因。通过实时定量聚合酶链反应分析，GRB10过度表达，并且通过对胰岛素样生长因子1（IGF1）和胰岛素样生长因子结合蛋白 - 3（IGFBP3）进行酶联免疫吸附测定，我们发现该患者的IGF1和IGFBP3低表达。 我们证明，可以对与特定出生缺陷的分子基础相关的不常见、罕见和特殊的分子缺陷组合进行分析和诊断，从而有可能解释所观察到的分子缺陷组合的变异性。 本文的网络版（doi:10.1186/s13023 - 016 - 0465 - 4）包含补充材料，授权用户可获取。