Intestinal current measurement for diagnostic classification of patients with questionable cystic fibrosis: validation and reference data

Derichs, Nico; Sanz, Javier; Känel, Thomas von; Stolpe, C.; Zapf, Antonia; Tümmler, Burkhard; Gallati, Sabina; Ballmann, Manfred

doi:10.1136/thx.2009.125088

Cited by 125 publications

(119 citation statements)

References 32 publications

Supporting

Mentioning

105

Contrasting

Unclassified

Order By: Relevance

“…Notably, defects in CFTR-mediated chloride transport correlated with CF disease severity, suggesting that ICM accurately reflects the level of CFTR functionality. Moreover, pancreatic insufficient patients with Class I-III mutations had absent or minimal chloride secretion; a high amount of residual function was observed in pancreatic sufficient CF patients with Class IV-V mutations and normal CFTR function was noted in heterozygotes and healthy controls [64].…”

Section: Cftr Correctorsmentioning

confidence: 99%

“…The degree of CFTR activity in the intestine can be measured using an electrophysiological test: the intestinal current measurement (ICM) [62]. Studies have shown that ICM correlates with CFTR genotype and phenotype [63], and diagnostic sensitivity in difficult CF diagnosis remarkably reaches 100% [64], making this tool also a potentially useful CF biomarker. Notably, defects in CFTR-mediated chloride transport correlated with CF disease severity, suggesting that ICM accurately reflects the level of CFTR functionality.…”

Section: Cftr Correctorsmentioning

confidence: 99%

See 1 more Smart Citation

Targeting a genetic defect: cystic fibrosis transmembrane conductance regulator modulators in cystic fibrosis

Derichs

2013

Eur Respir Rev

Self Cite

105

View full text Add to dashboard Cite

Cystic fibrosis (CF) is caused by genetic mutations that affect the cystic fibrosis transmembrane conductance regulator (CFTR) protein. These mutations can impact the synthesis and transfer of the CFTR protein to the apical membrane of epithelial cells, as well as influencing the gating or conductance of chloride and bicarbonate ions through the channel. CFTR dysfunction results in ionic imbalance of epithelial secretions in several organ systems, such as the pancreas, gastrointestinal tract, liver and the respiratory system. Since discovery of the CFTR gene in 1989, research has focussed on targeting the underlying genetic defect to identify a disease-modifying treatment for CF. Investigated management strategies have included gene therapy and the development of small molecules that target CFTR mutations, known as CFTR modulators. CFTR modulators are typically identified by high-throughput screening assays, followed by preclinical validation using cell culture systems. Recently, one such modulator, the CFTR potentiator ivacaftor, was approved as an oral therapy for CF patients with the G551D-CFTR mutation. The clinical development of ivacaftor not only represents a breakthrough in CF care but also serves as a noteworthy example of personalised medicine.

show abstract

Section: Cftr Correctorsmentioning

confidence: 99%

Section: Cftr Correctorsmentioning

confidence: 99%

Targeting a genetic defect: cystic fibrosis transmembrane conductance regulator modulators in cystic fibrosis

Derichs

2013

Eur Respir Rev

Self Cite

105

View full text Add to dashboard Cite

show abstract

“…Nach der DNA-Extraktion aus den Trockenblutkarten werden die [64] oder NPD (Transepithelial Nasal potential difference) [20] hilfreich sein. Diese Verfahren sind jedoch nur in speziellen Zentren wie Hannover oder Heidelberg möglich und nur z.T.…”

Section: Genetische Diagnostik Des Mukoviszidosescreeningsunclassified

Einführung des deutschlandweiten Neugeborenenscreenings für Mukoviszidose

Heinemann

Hentschel

Becker

et al. 2016

LaboratoriumsMedizin

View full text Add to dashboard Cite

ZusammenfassungDie Mukoviszidose oder Cystische Fibrose (CF) ist eine autosomal rezessiv vererbte Stoffwechselerkrankung und mit einer regional schwankenden Inzidenz von ca. 1:3.300–1:5.800 eine der häufigsten angeborenen Stoffwechselerkrankungen in Deutschland. Durch eine mutationsbedingte verminderte oder fehlende Funktion von Chloridkanälen kommt es hier zu einer Veränderung der Sekretzusammensetzung aller exokrinen Drüsen. Die mittlere Lebenserwartung von Mukoviszidose-Patienten konnte durch verbesserte Behandlungsstrategien auf mittlerweile über 40 Jahre erheblich gesteigert werden. Es hat sich dabei gezeigt, dass eine frühzeitige Diagnosestellung einen positiven Einfluss auf Krankheitsverlauf, Lebensqualität und Lebenserwartung der betroffenen Patienten hat. Diese Erkenntnis führte in den letzten 10 Jahren europaweit zur Aufnahme der Mukoviszidose in regionale und nationale Neugeborenenscreening-Programme. Mit dem Beschluss des Gemeinsamen Bundesausschusses zur Einführung des Mukoviszidosescreenings im August 2015 wurde Mukoviszidose nun auch in Deutschland als weitere Zielkrankheit in die Kinderrichtlinien aufgenommen und ist nach Veröffentlichung im Bundesanzeiger somit bundeseinheitlich als Bestandteil des deutschen Neugeborenenscreening-Programms vorgeschrieben. Das Procedere beinhaltet ein Stufenscreening mit der Kombination von Immunreaktivem Trypsin (IRT) und Pankreatitis-assoziiertem Protein (PAP) mit zusätzlicher Mutationsanalytik. Dank einer deutschlandweit früheren Diagnosestellung wird ein verbessertes Langzeitoutcome von Mukoviszidose-Patienten erwartet.

show abstract

“…The researchers found that the cumulative chloride secretory response of ΔI sc,carbachol , ΔI sc,cAMP/forskolin and ΔI sc,histamine was the best diagnostic ICM parameter, differentiating patients with questionable CF into pancreatic-sufficient-CF and 'CF unlikely' groups. The study underlines the diagnostic value of ICM, especially for confirmation of CF in the absence of two disease-causing CFTR mutations, exclusion of CF despite intermediate sweat test and age groups unsuitable for NPD measurements (Derichs et al, 2010). They conclude that ICM is an important tool for functional assessment in CFTR mutations of unknown clinical relevance (Derichs et al, 2010).…”

Section: Intestinal Current Measurement (Icm) As a Diagnostic Tool Fomentioning

confidence: 99%

“…There is information in the literature about the use of ICM as a clinical diagnostic tool (De Jonge et al, 2004;Hug et al, 2004). Derichs et al (2010) described reference values and validated ICM for the diagnostic classification of questionable CF at all patient ages. The ICM method was performed in 309 rectal biopsies from 130 infants, children and adults including patients with known pancreatic-insufficient, pancreaticsufficient, patients with an unclear diagnosis with mild CF symptoms, intermediate sweat test and/or CFTR mutation screening and healthy controls.…”

Section: Intestinal Current Measurement (Icm) As a Diagnostic Tool Fomentioning

confidence: 99%

Biochemical and Molecular Genetic Testing Used in the Diagnosis and Assessment of Cystic Fibrosis

McGrowder¹

2012

Cystic Fibrosis - Renewed Hopes Through Research

View full text Add to dashboard Cite

Intestinal current measurement for diagnostic classification of patients with questionable cystic fibrosis: validation and reference data

Cited by 125 publications

References 32 publications

Targeting a genetic defect: cystic fibrosis transmembrane conductance regulator modulators in cystic fibrosis

Targeting a genetic defect: cystic fibrosis transmembrane conductance regulator modulators in cystic fibrosis

Einführung des deutschlandweiten Neugeborenenscreenings für Mukoviszidose

Biochemical and Molecular Genetic Testing Used in the Diagnosis and Assessment of Cystic Fibrosis

Contact Info

Product

Resources

About