Open AccessFunctional analysis of the p.[Arg74Trp;Val201Met;Asp1270Asn]/p.Phe508del CFTR mutation genotype in human native colon
Author(s) -
Schucht Sylvia,
Minso Rebecca,
Lex Christiane,
Reiss Jochen,
Stanke Frauke,
Tamm Stephanie,
van Barneveld Andrea,
Tümmler Burkhard
Publication year - 2019
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.526
Subject(s) - genotype , phenotype , allele , compound heterozygosity , mutation , biology , genetics , microbiology and biotechnology , medicine , gene
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.