评估非白人囊性纤维化患者中非诊断性 CFTR 基因型中的上皮钠离子通道变体。

Assessment of epithelial sodium channel variants in nonwhite cystic fibrosis patients with non-diagnostic CFTR genotypes.

机构信息

Department of Pathology, Stanford University Medical Center, Stanford, CA 94305, USA.

Department of Pathology, Stanford University Medical Center, Stanford, CA 94305, USA; Department of Pediatrics, Stanford University Medical Center, Stanford, CA 94305, USA.

出版信息

J Cyst Fibros. 2016 Jan;15(1):52-9. doi: 10.1016/j.jcf.2015.04.001. Epub 2015 Apr 18.

DOI:10.1016/j.jcf.2015.04.001

PMID:25900089

Abstract

PURPOSE

Several lines of evidence suggest a role for the epithelial sodium channel (ENaC) in cystic fibrosis (CF). The purpose of our study was to assess the contribution of genetic variants in the ENaC subunits (α, β, γ) in nonwhite CF patients in whom CFTR molecular testing has been non-diagnostic.

METHODS

Samples were obtained from patients who were nonwhite and whose molecular CFTR testing did not identify two mutations. Sequencing of the SCNN1A, B, and G genes was performed and variants assessed for pathogenicity and association with CF using databases, protein and splice site mutation analysis software, and literature review.

RESULTS

We identified four nonsynonymous amino acid variants in SCNN1A, three in SCNN1B and one in SCNN1G. There was no convincing evidence of pathogenicity. Whereas all have been reported in the dbSNP database, only p.Ala334Thr, p.Val573Ile, and p.Thr663Ala in SCNN1A, p.Gly442Val in SCNN1B and p.Gly183Ser in SCNN1G were previously reported in ENaC genetic studies of CF or CF-like patients. Synonymous substitutions were also observed but novel synonymous variants were not detected.

CONCLUSION

There is no conclusive association of ENaC genetic variants with CF in nonwhite CF patients.

摘要

目的

有几条证据表明上皮钠通道（ENaC）在囊性纤维化（CF）中起作用。我们研究的目的是评估 ENaC 亚基（α、β、γ）中的遗传变异在 CFTR 分子检测无诊断结果的非白人 CF 患者中的贡献。

方法

从非白人患者中获取样本，这些患者的分子 CFTR 检测未发现两种突变。对 SCNN1A、B 和 G 基因进行测序，并使用数据库、蛋白质和剪接位点突变分析软件以及文献综述评估变体的致病性和与 CF 的关联。

结果

我们在 SCNN1A 中发现了四个非同义氨基酸变异，在 SCNN1B 中发现了三个，在 SCNN1G 中发现了一个。没有令人信服的致病性证据。虽然所有这些都在 dbSNP 数据库中报道过，但只有 SCNN1A 中的 p.Ala334Thr、p.Val573Ile 和 p.Thr663Ala，SCNN1B 中的 p.Gly442Val 和 SCNN1G 中的 p.Gly183Ser 在 CF 或 CF 样患者的 ENaC 遗传研究中以前被报道过。还观察到同义替换，但未检测到新的同义变体。