Clinical efficacy of CFTR modulator therapy in people with cystic fibrosis carrying the I1234V mutation.

Background: The cystic fibrosis transmembrane conductance regulator (CFTR) mutation I1234V (I1234V, p.Ile1234Val, c.3700A>G), is a missense-mutation that creates a cryptic splice site, with the formation of a protein lacking 6 amino acids, that is misfolded and misprocessed.

Clinical impact of exome sequencing in the setting of a general pediatric ward for hospitalized children with suspected genetic disorders.

Genetic conditions contribute a significant portion of disease etiologies in children admitted to general pediatric wards worldwide. While exome sequencing (ES) has improved clinical diagnosis and management over a variety of pediatric subspecialties, it is not yet routinely used by general pediatric hospitalists. We aim to investigate the impact of exome sequencing in sequencing-naive children suspected of having monogenic disorders while receiving inpatient care.

Spontaneous pneumothorax-When do we need to intervene?

Background: Pneumothorax can be classified as traumatic, iatrogenic or spontaneous (SP), which can be subdivided into primary spontaneous pneumothorax (PSP), a condition without preexisting lung disease, or secondary spontaneous pneumothorax (SSP) a complication of a preexisting lung disease. Recurrence rate of PSP is 30% whereas for SSP rate is unknown. This article explores the experience of a tertiary center over 20 years.

Clinical, neuroimaging, and molecular spectrum of TECPR2-associated hereditary sensory and autonomic neuropathy with intellectual disability.

Bi-allelic TECPR2 variants have been associated with a complex syndrome with features of both a neurodevelopmental and neurodegenerative disorder. Here, we provide a comprehensive clinical description and variant interpretation framework for this genetic locus. Through international collaboration, we identified 17 individuals from 15 families with bi-allelic TECPR2-variants.

Advanced Lung Disease in Patients with Cystic Fibrosis Is Associated with Low Diffusion capacity.

Background: The single-breath diffusing capacity of the lungs (DLCOSB) test measures the extent to which carbon monoxide (CO) passes from the lung air sacs into the blood. The accessible alveolar volume (VASB) is measured by inert gas during a 10-second period. The single-breath transfer coefficient of the lung for carbon monoxide (KCOSB) is the DLCOSB divided by VASB.

Phenotypic and molecular characteristics of CF patients carrying the I1234V mutation.

Background: The Mutation I1234V is a CF causing mutation; however the mechanisms leading to loss of function are not fully understood. In this study, we aimed to characterize phenotypically individuals with the I1234V variant, and to gain a structural point of view of the mutant CFTR using computational studies.

Methods: We conducted a retrospective descriptive study, reviewing the clinical records of 9 Israeli patients.

Correction to: Ambulatory blood pressure profiles in familial dysautonomia.

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Resting Energy Expenditure in Patients With Familial Dysautonomia: A Preliminary Study.

Objectives: Familial dysautonomia (FD) is a rare hereditary sensory and autonomic neuropathy characterized by chronic lung disease and cyclic vomiting due to hyper-adrenergic crises. Most FD patients are in a depleted nutritional state; however, the phenotype of the disease is quite different between patients, as for the severity of lung disease and the intensity and frequency of these pathognomonic crises. In this study we wanted to investigate whether resting energy expenditure (REE) levels are increased in this population, and if correlations exist between REE levels and phenotype severity.

Respiratory care in familial dysautonomia: Systematic review and expert consensus recommendations.

Background: Familial dysautonomia (Riley-Day syndrome, hereditary sensory autonomic neuropathy type-III) is a rare genetic disease caused by impaired development of sensory and afferent autonomic nerves. As a consequence, patients develop neurogenic dysphagia with frequent aspiration, chronic lung disease, and chemoreflex failure leading to severe sleep disordered breathing. The purpose of these guidelines is to provide recommendations for the diagnosis and treatment of respiratory disorders in familial dysautonomia.

Omalizumab in allergic bronchopulmonary aspergillosis in patients with cystic fibrosis.

Background: Allergic bronchopulmonary aspergillosis (ABPA) is a condition characterized by a Th2 response, serum eosinophilia, and increased total serum IgE to . ABPA occurs in cystic fibrosis (CF) and asthma. Omalizumab is a humanized recombinant monoclonal antibody against IgE.

Ambulatory blood pressure profiles in familial dysautonomia.

Objective: Familial dysautonomia (FD) is a rare genetic disease that involves extreme blood pressure fluctuations secondary to afferent baroreflex failure. The diurnal blood pressure profile, including the average, variability, and day-night difference, may have implications for long-term end organ damage. The purpose of this study was to describe the circadian pattern of blood pressure in the FD population and relationships with renal and pulmonary function, use of medications, and overall disability.

A Controlled Trial of Inhaled Bronchodilators in Familial Dysautonomia.

Background: Chronic lung disease is a leading cause of premature death in patients with familial dysautonomia (FD). A significant number of patients have obstructive airway disease, yet it is not known whether this is pharmacologically reversible.

Methods: We conducted a double-blind, placebo-controlled, randomized clinical trial comparing the beta 2 agonist albuterol with the muscarinic blocker ipratropium bromide in patients homozygous for the IKBKAP founder mutation.

Ivacaftor for the p.Ser549Arg (S549R) gating mutation - The Israeli experience.

Background: Ivacaftor is a drug that increases the probability of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel remaining open. Information about the efficacy of ivacaftor in patients carrying the rare p.Ser549Arg (S549R) CFTR mutation is sparse.

Consequences of Expiratory Flow Limitation at Rest in Subjects with Cystic Fibrosis.

Rationale: Expiratory flow limitation at resting tidal volume (EFLTV) presents a severe mechanical constraint in chronic lung diseases and has not yet been studied longitudinally in cystic fibrosis.

Objectives: To study the effect of EFLTV as it emerged from simple spirometry on lung function and clinical status in cystic fibrosis.

Methods: Best year spirometry that included tidal flow/volume curves and the related clinical data were retrospectively collected over 12 ± 3.

FVC deterioration, airway obstruction determination, and life span in Ataxia telangiectasia.

Rationale: Forced vital capacity (FVC) values decrease with progress of the disease in Ataxia telangiectasia (AT).

Objective: To study the effect of this process on airway obstruction determination and life span in AT.

Methods: Clinical data and yearly best spirometry maneuvers were collected retrospectively from 37 AT patients (196 spirometry tests) during 5.

Several siblings with Cystic Fibrosis as a risk factor for poor outcome.

Background: Occurrence of Cystic Fibrosis (CF) in more than one member in a family is not uncommon. The aim of our study was to assess the influence of multiple siblings with CF on disease expression and outcome.

Methods: Study group consisted of 2-siblings (2-sibs, n = 42) or 3/4 siblings (3/4-sibs, n = 22) with CF in one family.