Mild cystic fibrosis in patients with the rare P5L CFTR mutation

Spicuzza, Lucia; Sciuto, C.; Dio, Lucia Di; Mattina, Teresa; Leonardi, ﻿Salvatore; Giudice, Michele Miraglia Del; Rosa, Mario La

doi:10.1016/j.jcf.2011.08.009

Cited by 4 publications

(3 citation statements)

References 15 publications

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“…Patients with P5L in association with a severe class II mutation, may be asymptomatic or affected by a “mild” CF. As in patient 2, P5L has already been described in trans with F508del in five subjects, for three of them, dehydration remains the sole manifestation of an altered channel activity . This variation of CFTR gene seems not so rare and has been recently added to the CFTR2 database.…”

Section: Lessons Learnedmentioning

confidence: 67%

Should isolated Pseudo‐Bartter syndrome be considered a CFTR‐related disorder of infancy?

Poli

Rose

Timpano

et al. 2019

Pediatric Pulmonology

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Background Infants that are negative to cystic fibrosis (CF) newborn screening (NBS) programs, or in countries without NBS, may present with metabolic alkalosis and severe salt depletion, a well‐known clinical manifestation of CF termed Pseudo‐Bartter syndrome (PBS). Here, we report the cases of three CF‐negative children, who carry rare mutations in the CF transmembrane conductance regulator (CFTR) gene, and, for whom, PBS was the only manifestation of CFTR protein dysfunction. There is no diagnostic label for these cases. Methods Medical records of patients followed at our Cystic Fibrosis Centre were revised and data were collected for all patients who presented with an isolated PBS. The syndrome was defined as an episode of dehydration with low levels of serum sodium (<134mmol/L), potassium ( <3.4mmol/L), and chloride ( <100mmol/L), with metabolic alkalosis (bicarbonatemia >27mmol/L) in the absence of renal tubulopathy. Results Three out of 73 (4%) CF infants presented with a severe metabolic alkalosis with salt depletion; two of these required admission to the intensive care unit. Two infants had a negative NBS, and one was identified as a CF carrier. Sweat test was repeatedly in the negative/borderline ranges for all patients. Less than two CF causing mutations were identified (F508del/R1070W, F508del; L467F/P5L, R1066H/P5L). During a mean follow‐up of 9 years, the children had no other CF manifestations. Conclusion We suggest that PBS as the sole manifestation of CFTR dysfunction might be considered a CFTR‐related disorder of infancy.

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Section: Lessons Learnedmentioning

confidence: 67%

Should isolated Pseudo‐Bartter syndrome be considered a CFTR‐related disorder of infancy?

Poli

Rose

Timpano

et al. 2019

Pediatric Pulmonology

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“…R1070W mutation has been associated with mild pancreatic insufficiency and obstructive azoospermia. There are 140 cases in the world with the R1070W mutation [4,6,12,13].…”

Section: Mutations In a Single Gene -The Cystic Fibrosis Transmembranementioning

confidence: 99%

Cystic Fibrosis - An Open Book that must be Always Updated

Sur¹

2014

J Genet Syndr Gene Ther

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Cystic fibrosis (CF) is the most common autosomal recessive disease in Caucasians. The dysfunction of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) causes the disease by disrupting epithelial salt and water transport. Characteristic manifestations of the disease such as chronic respiratory infections, pancreatic enzyme insufficiency, and infertility are caused by the accumulation of mucus in the ducts. Nowadays nearly 2000 CFTR mutatioans are known. The most common mutation is F508del. F508del/F508del mutation is not always accompanied by severe manifestations. The clinical expression is different among patients, taking into account the mutations and another factor, among them, enviromental and modifier genes. In the case of rare mutations symptoms vary from patient to patient being influenced by environmental factors and modifier genes. We present a case with a less common combination of mutations and an atypical clinical presentation.

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“…CF is a classically inherited autosomal recessive condition whereby two faulty copies of the gene are necessary to develop CF. The severity of the disease can vary greatly and depends on a wide range of factors including the combination of mutations that someone inherits [15,16]. People with one faulty copy of the CFTR gene are carriers but do not display any symptoms.…”

Section: Introductionmentioning

confidence: 99%

Identifying children with Cystic Fibrosis in population-scale routinely collected data in Wales

Griffiths

Schlüter

Akbari

et al. 2020

IJPDS

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Introduction The challenges in identifying a cohort of people with a rare condition can be addressed by routinely collected, population-scale electronic health record (eHR) data, which provide large volumes of data at a national level. This paper describes the challenges of accurately identifying a cohort of children with Cystic Fibrosis (CF) using eHR and their validation against the UK CF Registry. Objectives To establish a proof of principle and provide insight into the merits of linked data in CF research and the benefits of access to multiple data sources. In particular, the UK CF Registry data, and to demonstrate the opportunity it represents as a resource for future CF research. Method Three eHR data sources were used to identify children with CF born in Wales between 1st January 1998 and 31st August 2015 within the Secure Anonymised Information Linkage (SAIL) Databank. The UK CF Registry was later acquired by SAIL and linked to the eHR cohort to validate the cases and explore the reasons for misclassifications. Results We identified 352 children with CF in the three eHR data sources. This was greater than expected based on historical incidence rates in Wales. Subsequent validation using the UK CF Registry found that 257 (73%) of these were true cases. Over 98% of individuals identified as CF cases in all three eHR data sources were confirmed as true cases; but this was only the case for 19.8% of those identified in a single data source. Conclusion Identifying health conditions in eHR data can be challenging, so data quality assurance and validation is important or the merit of the research is undermined. This retrospective review identifies some of the challenges in identifying CF cases and demonstrates the benefits of linking cases across multiple data sources to improve quality.

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Mild cystic fibrosis in patients with the rare P5L CFTR mutation

Cited by 4 publications

References 15 publications

Should isolated Pseudo‐Bartter syndrome be considered a CFTR‐related disorder of infancy?

Should isolated Pseudo‐Bartter syndrome be considered a CFTR‐related disorder of infancy?

Cystic Fibrosis - An Open Book that must be Always Updated

Identifying children with Cystic Fibrosis in population-scale routinely collected data in Wales

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