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Orphanet Journal of Rare Diseases

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Open Access 01-12-2017 | Research

What can the CF registry tell us about rare CFTR-mutations? A Belgian study

Authors: E. De Wachter, M. Thomas, S. S. Wanyama, S. Seneca, A. Malfroot

Published in: Orphanet Journal of Rare Diseases | Issue 1/2017

Abstract

Background

CFTR2 provides clinical and functional information of the most common CFTR-mutations. Rare mutations (RMs) occur in only a few patients with limited reported clinical data. Their role in CF-disease liability is hardly documented.

Methods

Belgian CF-Registry 2013 data were analyzed to identify CF with at least 1 RM (CF_+RM). Clinical data and sweat chloride of CF_+RM were compared to CF-controls, carrying 2 class 1 to 3 mutations (CF_classic). Disease severity was compared between both groups. To avoid bias in the comparison, transplanted patients were excluded from each group.

Results

Seventy-seven CF_+RM were identified (77/1183 = 6.5%). Sixty-four different RM were detected, of which 21 had not been previously reported. All RMs, corresponding to HGVS (Human Genome Variation Society) nomenclature, were listed in supplementary data.

Seven transplanted CF_+RM were excluded for further analysis. CF_+RM had higher age at diagnosis [median (IQR)] [3.7 y (0.3–18.3) vs. 0.3y (0.1–2,0) (p < 0.0001)], lower sweat chloride [96 mmol/L (64–107) vs. 104 mmol/L (97–115) (p < 0.0001)], higher FEV₁%pred [77%pred (58–96) vs. 68%pred (48–86) (p = 0.017)], were less frequently pancreatic insufficient [56% vs. 98% (p < 0.0001)], Pseudomonas aeruginosa colonized [24% vs. 44% (p = 0.0093)] and needed fewer IV antibiotics [36% vs. 51% (p = 0.041)] than CF_classic. However, a wide spectrum of disease severity was seen amongst CF_+RM.

Conclusions

CF-patients with a RM cover 6.5% of the Belgian CF-population. Rare mutations can be found in severely ill patients, but more often in late diagnosed, pancreatic sufficient patients.

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Title: What can the CF registry tell us about rare CFTR-mutations? A Belgian study
Authors: E. De Wachter
M. Thomas
S. S. Wanyama
S. Seneca
A. Malfroot
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: Orphanet Journal of Rare Diseases / Issue 1/2017
Electronic ISSN: 1750-1172
DOI: https://doi.org/10.1186/s13023-017-0694-1

At a glance: The STEP trials

Springer Medicine

What can the CF registry tell us about rare CFTR-mutations? A Belgian study

Abstract

Background

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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