Identification of a novel RPGR mutation associated with retinitis pigmentosa and primary ciliary dyskinesia in a Slovak family: a case report

BackgroundThe mutations in the RPGR (retinitis pigmentosa GTPase regulator) gene are the most common cause of X-linked retinitis pigmentosa (XLRP), a rare genetic disorder affecting the photoreceptor cells in the retina. Several reported cases identified this gene as a genetic link between retinitis pigmentosa (RP) and primary ciliary dyskinesia (PCD), characterised by impaired ciliary function predominantly in the respiratory tract. Since different mutations in the same gene can result in various clinical manifestations, it is important to describe a correlation between the gene variant and the observed phenotype.MethodsTwo young brothers from a non-consanguineous Slovak family with diagnosed retinal dystrophy and recurrent respiratory infections were examined. Suspected PCD was diagnosed based on a PICADAR questionnaire, nasal nitric oxide analysis, transmission electron microscopy, high-speed video microscopy analysis, and genetic testing.ResultsWe identified a novel frameshift RPGR mutation NM_001034853: c.309_310insA, p.Glu104Argfs*12, resulting in a complex X-linked phenotype combining PCD and RP. In our patients, this mutation was associated with normal ultrastructure of respiratory cilia, reduced ciliary epithelium, more aciliary respiratory epithelium, shorter cilia, and uncoordinated beating with a frequency at a lower limit of normal beating, explaining the clinical manifestation of PCD in our patients.ConclusionThe identified novel pathogenic mutation in the RPGR gene expands the spectrum of genetic variants associated with the X-linked PCD phenotype overlapping with RP, highlighting the diversity of mutations contributing to the disorder. The described genotype–phenotype correlation can be useful in clinical practice to recognise a broader spectrum of PCD phenotypes as well as for future research focused on the genetic basis of PCD, gene interactions, the pathways implicated in PCD pathogenesis, and the role of RPGR protein for the proper functioning of cilia in various tissues throughout the body

Young and exhausted

Chronic Fatigue Syndrome (CFS), also known as myalgic encephalomyelitis (ME), is a complicated disease characterized by extreme fatigue of at least six months duration. It is necessary to rule out the organic cause of CFS in the pediatric patient in order not to overlook the preventable or the treatable condition. In our case report we present a case of a patient with a surprising origin OF CFS/ME diagnosed by cardiopulmonary exercise testin

Sleep architecture in children with common phenotype of obstructive sleep apnea

STUDY OBJECTIVES: In children, the effect of the common phenotype of obstructive sleep apnea (OSA) on sleep architecture is not adequately documented. The aim of this study was to evaluate sleep architecture in a pediatric population with the common phenotype of OSA. METHODS: The prospective cross-sectional study included 116 children in the age range of 3 to 8 years with suspected OSA and 51 healthy children. All children underwent standard overnight in-laboratory video polysomnography. Patients with obstructive apnea-hypopnea index ≥ 1, adenotonsillar hypertrophy, a long face, narrow palate or minor malocclusions, and no obesity were defined as a common phenotype. Polysomnographic parameters of sleep architecture and sleep clinical record were statistically analyzed according to OSA and its severity. RESULTS: In total, 94 pediatric patients (59.60% male) received the diagnosis of the common phenotype of OSA (mean age of 5.25 ± 1.39 years). A lower percentage of stage N3 sleep (27.70 ± 3.76% versus 31.02 ± 4.23%; P < .05), a greater percentage of stage N1 sleep (8.40 ± 3.98% versus 2.68 ± 3.02%, P < .01), reduced deep sleep efficiency (46.01 ± 4.98% versus 50.25 ± 3.72%; P < .05) and longer sleep latency (18.40 ± 8.48 minutes versus 9.90 ± 11.55 minutes, P < .01) were found in children with the common phenotype of OSA compared with healthy controls. No significant differences were found in total sleep time, sleep efficiency, and percentage of stage R sleep and stage N2 sleep between groups and in sleep stage distribution and cyclization. CONCLUSIONS: These findings suggest that the most common phenotype of pediatric OSA has a negative effect on the structure of sleep, but other clinical studies are needed to confirm this result

Dysfunctional mucociliary clearance in asthma and airway remodeling – New insights into an old topic

Bronchial asthma is a heterogeneous respiratory condition characterized by chronic airway inflammation, airway hyperresponsiveness and airway structural changes (known as remodeling). The clinical symptoms can be evoked by (non)specific triggers, and their intensity varies over time. In the past, treatment was mainly focusing on symptoms’ alleviation; in contrast modern treatment strategies target the underlying inflammation, even during asymptomatic periods. Components of airway remodeling include epithelial cell shedding and dysfunction, goblet cell hyperplasia, subepithelial matrix protein deposition, fibrosis, neoangiogenesis, airway smooth muscle cell hypertrophy and hyperplasia. Among the other important, and frequently forgotten aspects of airway remodeling, also loss of epithelial barrier integrity, immune defects in anti-infectious defence and mucociliary clearance (MCC) dysfunction should be pointed out. Mucociliary clearance represents one of the most important defence airway mechanisms. Several studies in asthmatics demonstrated various dysfunctions in MCC – e.g., ciliated cells displaying intracellular disorientation, abnormal cilia and cytoplasmic blebs. Moreover, excessive mucus production and persistent cough are one of the well-recognized features of severe asthma and are also associated with defects in MCC. Damaged airway epithelium and impaired function of the ciliary cells leads to MCC dysfunction resulting in higher susceptibility to infection and inflammation. Therefore, new strategies aimed on restoring the remodeling changes and MCC dysfunction could present a new therapeutic approach for the management of asthma and other chronic respiratory diseases.</p