人类天然结肠中p.[精氨酸74;缬氨酸201;天冬氨酸1270]/p.苯丙氨酸508缺失CFTR突变基因型的功能分析
Functional analysis of the p.[Arg74Trp;Val201Met;Asp1270Asn]/p.Phe508del CFTR mutation genotype in human native colon.
作者信息
Schucht Sylvia, Minso Rebecca, Lex Christiane, Reiss Jochen, Stanke Frauke, Tamm Stephanie, van Barneveld Andrea, Tümmler Burkhard
机构信息
Pediatric Pulmonary and Allergology Outpatient Clinic, Paediatric Cardiology and Intensive Care Medicine, Universitätsmedizin Göttingen, Göttingen, Germany.
Clinical Research Group 'Molecular Pathology of Cystic Fibrosis', Clinic for Paediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.
出版信息
Mol Genet Genomic Med. 2019 Feb;7(2):e00526. doi: 10.1002/mgg3.526. Epub 2019 Jan 1.
BACKGROUND
The impact of complex alleles on CFTR processing and function has yet not been investigated in native human tissue.
METHODS
Intestinal current measurements (ICM) followed by CFTR immunoblot were performed on rectal biopsies taken from two siblings who are compound heterozygous for the CFTR mutations p.Phe508del and the complex allele p.[Arg74Trp;Val201Met;Asp1270Asn].
RESULTS
Normal and subnormal chloride secretory responses in the ICM were associated with normal and fourfold reduced amounts of the mature glycoform band C CFTR, respectively, consistent with the unequal clinical phenotype of the siblings.
CONCLUSION
The combined use of bioassay and protein analysis is particularly meaningful to resolve the CFTR phenotype of "indeterminate" borderline CFTR genotypes on a case-to-case basis.
背景
复杂等位基因对囊性纤维化跨膜传导调节因子（CFTR）加工和功能的影响尚未在人体原生组织中进行研究。
方法
对两名分别为CFTR突变p.Phe508del和复杂等位基因p.[Arg74Trp;Val201Met;Asp1270Asn]的复合杂合子的兄弟姐妹的直肠活检组织进行肠电流测量（ICM），随后进行CFTR免疫印迹分析。
结果
ICM中正常和低于正常的氯化物分泌反应分别与成熟糖基化形式的带C CFTR正常量和减少四倍的量相关，这与兄弟姐妹不相等的临床表型一致。
结论
生物测定和蛋白质分析的联合使用对于逐案解决“不确定”的临界CFTR基因型的CFTR表型特别有意义。
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