Novel variants in TECRL cause recessive inherited CPVT type 3 with severe and variable clinical symptoms.

INTRODUCTION: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome characterized by adrenergically stimulated ventricular tachycardia. The most common form of CPVT is due to autosomal dominant variants in the cardiac ryanodine-receptor gene (RYR2). However, trans-2,3-enoyl-CoA reductase-like (TECRL) was recently suggested to be a novel candidate gene for life-threatening inherited arrhythmias. Patients previously reported with pathogenic changes in TECRL showed a special mixed phenotype of CPVT and long-QT-syndrome (LQTS) termed CPVT type 3 (CPVT3), an autosomal recessive disorder. METHODS AND RESULTS: We implemented TECRL into our NGS panel diagnostics for CPVT and LQTS in April 2017. By December 2018, 631 index patients with suspected CPVT or LQTS had been referred to our laboratory for genetic testing. Molecular analysis identified four Caucasian families carrying novel variants in TECRL. One patient was homozygous for Gln139* resulting in a premature stop codon and loss-of-function of the TECRL protein. Another patient was homozygous for Pro290His, probably leading to an altered folding of the 3-oxo-5-alpha steroid 4-dehydrogenase domain of the TECRL protein. The LOF-variant Ser309* and the missense-variant Val298Ala have been shown to be compound heterozygous in another individual. NGS-based copy number variation analysis and quantitative PCR revealed a quadruplication of TECRL in the last individual, which is likely to be a homozygous duplication. CONCLUSION: The data from our patient collective indicate that CPVT3 occurs much more frequently than previously expected. Variants in TECRL may be causative in up to 5% of all CPVT cases. According to these findings, the default analysis of this gene is recommended if CPVT is suspected.

The impact of nasal aspiration with an automatic device on upper and lower respiratory symptoms in wheezing children: a pilot case-control study.

BACKGROUND: The impact of proper aspiration of nasal secretions during upper respiratory infection on the frequency and severity of symptoms of lower airways has never been investigated. The study was aimed at testing if cleaning the nasal cavities of children with recurrent wheezing using an automatic nasal aspirator improves the upper and lower respiratory symptoms during the cold season. METHODS: Parents of wheezing children (age 3-72 mo.) answered questionnaires and learned using a nebulizer equipped (cases) or not equipped (controls) with an automatic nasal aspirator (DuoBaby, OMRON, Japan). During a 90-days monitoring period parents filled an electronic diary (BreathMonitor, TPS, Rome, Italy) on their child's symptoms of the upper and lower airways. RESULTS: Eighty-nine/91 patients (43 cases, 46 controls) completed the study. Less days with upper (25.0% vs 46.4%, p = 0.004) or lower (21.8% vs 32.8%, p = 0.022) airways symptoms and less days with salbutamol inhalation (12.2% vs 16.9%, p < 0.001) were reported by cases than by controls. The episodes of upper respiratory symptoms were shorter [4.3 days (95%CI:3.8-4.9) vs 5.7 days (95%CI:5.0-6.4), p = 0.007] but not less frequent [2.3 (95%CI: 1.8-2.8) vs 2.6 (95%CI:2.2-3.0), p = 0.122] among cases than among controls. Similarly, the episodes of lower respiratory symptoms tended to be shorter [3.8 days, (95%CI: 3.4-4.2) vs 4.4 days, (95%CI: 4.4-6.0), p = 0.067] but not less frequent [1.9 (95%CI:1.5-2.3) vs 2.1 (95%CI:1.7-2.4), p = 0.240] among the group using the nasal aspirator. CONCLUSIONS: In our pilot study, the use of an automatic nasal aspirator in children with a history of recurrent wheezing was associated with an improved respiratory health during the cold season.

Correction to: The impact of nasal aspiration with an automatic device on upper and lower respiratory symptoms in wheezing children: a pilot case-control study.

The original article [1] contained a typesetting error in Table 5; this has now been corrected.