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Functional analysis of the p.[Arg74Trp;Val201Met;Asp1270Asn]/p.Phe508del CFTR mutation genotype in human native colon.

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.

SUBMITTER: Schucht S

PROVIDER: S-EPMC6393651 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Functional analysis of the p.[Arg74Trp;Val201Met;Asp1270Asn]/p.Phe508del CFTR mutation genotype in human native colon.

Schucht Sylvia S Minso Rebecca R Lex Christiane C Reiss Jochen J Stanke Frauke F Tamm Stephanie S van Barneveld Andrea A Tümmler Burkhard B

Molecular genetics & genomic medicine 20190101 2

<h4>Background</h4>The impact of complex alleles on CFTR processing and function has yet not been investigated in native human tissue.<h4>Methods</h4>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].<h4>Results</h4>Normal and subnormal chloride secretory responses in the ICM were associated with normal ...[more]

PMID: 30600599

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