RESUMEN
A non-consanguineous two-generation family of parent and monozygous twins who all three share the same CFTR mutation genotype p.Phe508del / p.Arg117His, was examined in clinical features, sweat test, nasal potential difference and intestinal current measurements. As expected the twins were very much alike in anthropometry and appearance and shared the clinical manifestation of CFTR dysfunction albeit at different intensity but unexpectedly like in comparison to their mother they were discordant in their CFTR-mediated basic defect and the response thereof to CFTR potentiation by ivacaftor. This case report illustrates the strong impact of non-inherited factors on the electrophysiological phenotype of the most common CFTR mutation genotype of variable clinical significance.
Asunto(s)
Regulador de Conductancia de Transmembrana de Fibrosis Quística , Fibrosis Quística , Aminofenoles , Benzodioxoles , Fibrosis Quística/diagnóstico , Fibrosis Quística/tratamiento farmacológico , Fibrosis Quística/genética , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Femenino , Genotipo , Humanos , Madres , Mutación , Núcleo FamiliarRESUMEN
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.