Diversity of the basic defect of homozygous CFTR mutation genotypes in humans

Stanke, F; Ballmann, M; Bronsveld, I; Dörk, T; Gallati, S; Laabs, U; Derichs, N; Ritzka, M; Posselt, H-G; Harms, H K; Griese, M; Blau, H; Mastella, G; Bijman, J; Veeze, H; Tümmler, B (2008). Diversity of the basic defect of homozygous CFTR mutation genotypes in humans. Journal of medical genetics, 45(1), pp. 47-54. London: BMJ Publishing Group 10.1136/jmg.2007.053561

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BACKGROUND: Knowledge of how CFTR mutations other than F508del translate into the basic defect in cystic fibrosis (CF) is scarce due to the low incidence of homozygous index cases. METHODS: 17 individuals who are homozygous for deletions, missense, stop or splice site mutations in the CFTR gene were investigated for clinical symptoms of CF and assessed in CFTR function by sweat test, nasal potential difference and intestinal current measurement. RESULTS: CFTR activity in sweat gland, upper airways and distal intestine was normal for homozygous carriers of G314E or L997F and in the range of F508del homozygotes for homozygous carriers of E92K, W1098L, R553X, R1162X, CFTRdele2(ins186) or CFTRdele2,3(21 kb). Homozygotes for M1101K, 1898+3 A-G or 3849+10 kb C-T were not consistent CF or non-CF in the three bioassays. 14 individuals exhibited some chloride conductance in the airways and/or in the intestine which was identified by the differential response to cAMP and DIDS as being caused by CFTR or at least two other chloride conductances. DISCUSSION: CFTR mutations may lead to unusual electrophysiological or clinical manifestations. In vivo and ex vivo functional assessment of CFTR function and in-depth clinical examination of the index cases are indicated to classify yet uncharacterised CFTR mutations as either disease-causing lesions, risk factors, modifiers or neutral variants.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine

UniBE Contributor:

Gallati, Sabina






BMJ Publishing Group




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Date Deposited:

04 Oct 2013 15:03

Last Modified:

17 Mar 2015 22:15

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https://boris.unibe.ch/id/eprint/27203 (FactScience: 104952)

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