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首页> 外文期刊>Molecular syndromology >Novel and Recurrent Mutations in the FGFR3 Gene and Double Heterozygosity Cases in a Cohort of Brazilian Patients with Skeletal Dysplasia
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Novel and Recurrent Mutations in the FGFR3 Gene and Double Heterozygosity Cases in a Cohort of Brazilian Patients with Skeletal Dysplasia

机译：巴西骨发育不良患者队列中FGFR3基因的新型和复发性突变以及双重杂合性病例

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Mutations in the fibroblast growth factor receptor 3 gene (iFGFR3/i) cause achondroplasia (ACH), hypochondroplasia (HCH), and thanatophoric dysplasia types I and II (TDI/TDII). In this study, we performed a genetic study of 123 Brazilian patients with these phenotypes. Mutation hotspots of the iFGFR3/i gene were PCR amplified and sequenced. All cases had recurrent mutations related to ACH, HCH, TDI or TDII, except for 2 patients. One of them had a classical TDI phenotype but a typical ACH mutation (c.1138GA) in combination with a novel c.1130TC mutation predicted as being pathogenic. The presence of the second c.1130TC mutation likely explained the more severe phenotype. Another atypical patient presented with a compound phenotype that resulted from a combination of ACH and X-linked spondyloepiphyseal dysplasia tarda (OMIM 313400). Next-generation sequencing of this patient's DNA showed double heterozygosity for a typical de novo ACH c.1138GA mutation and a maternally inheritedi TRAPPC2/i c.6del mutation. All mutations were confirmed by Sanger sequencing. A pilot study using high-resolution melting (HRM) technique was also performed to confirm several mutations identified through sequencing. We concluded that for recurrent iFGFR3/i mutations, HRM can be used as a faster, reliable, and less expensive genotyping test than Sanger sequencing.
机译：成纤维细胞生长因子受体3基因（ FGFR3 ）的突变会导致软骨发育不全（ACH），软骨发育不良（HCH）以及I型和II型肌痛性发育异常。在这项研究中，我们对123名具有这些表型的巴西患者进行了基因研究。 PCR扩增 FGFR3 基因的突变热点并测序。除2例患者外，所有病例均具有与ACH，HCH，TDI或TDII有关的复发性突变。其中一个具有经典的TDI表型，但具有典型的ACH突变（c.1138G> A）以及预计会致病的新型c.1130T> C突变。第二个c.1130T> C突变的存在可能解释了更严重的表型。另一位非典型患者表现出由ACH和X连锁性脊椎骨赘发育迟缓（OMIM 313400）联合产生的复合表型。该患者DNA的下一代测序显示典型的从头ACH c.1138G> A突变和母体遗传的 TRAPPC2 c.6del突变具有双重杂合性。通过Sanger测序证实所有突变。还进行了使用高分辨率熔解（HRM）技术的初步研究，以确认通过测序鉴定出的几个突变。我们得出的结论是，对于复发的 FGFR3 突变，与Sanger测序相比，HRM可以作为一种更快，更可靠且更便宜的基因分型测试。

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