Functional analysis of the p.[Arg74Trp;Val201Met;Asp1270Asn]/p.Phe508del CFTR mutation genotype in human native colon. Issue 2 (1st January 2019)

• Record Type: Journal Article
• Authors: Schucht, Sylvia; Minso, Rebecca; Lex, Christiane; Reiss, Jochen; Stanke, Frauke; Tamm, Stephanie; van Barneveld, Andrea; Tümmler, Burkhard
• Is Part Of: Molecular genetics & genomic medicine. Volume 7:Issue 2(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-01-01
• Subjects: CFTR bioassay -- CFTR immunoblot -- complex allele -- cystic fibrosis -- intestinal current measurement; Medical genetics -- Periodicals; Genomics -- Periodicals; 616.042
• DOI: 10.1002/mgg3.526
• Languages: English
• ISSNs: 2324-9269

Abstract

Abstract: 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. Abstract : The protein and functional phenotype of a complex CFTR allele of unknown clinical significance were characterized in native human tissue.