Defects of ciliogenesis have been implicated in a wide range of human phenotypes and play a crucial role in signal transduction and cell-cycle coordination. We used homozygosity mapping in two families with autosomal-recessive short-rib polydactyly syndrome Majewski type to identify mutations in NEK1 as an underlying cause of this lethal osteochondrodysplasia. NEK1 encodes a serine/threonine kinase with proposed function in DNA double-strand repair, neuronal development, and coordination of cell-cycle-associated ciliogenesis. We found that absence of functional full-length NEK1 severely reduces cilia number and alters ciliar morphology in vivo. We further substantiate a proposed digenic diallelic inheritance of ciliopathies by the identification of heterozygous mutations in NEK1 and DYNC2H1 in an additional family. Notably, these findings not only increase the broad spectrum of ciliar disorders, but suggest a correlation between the degree of defective microtubule or centriole elongation and organization and the severity of the resulting phenotype.

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Vaginal birth is associated with a large release of copeptin that exceeds all values published so far, including those in critically ill adult patients with shock or brain injury. Thus, vaginal birth is arguably the most intense stressor in life.

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Objective-To describe prenatal abnormalities of cardiac rhythm in patients with prolonged QT interval in the neonatal period. Design-A retrospective analysis of the results of fetal echocardiography and the outcome in patients with prolonged QT interval in the neonatal period who had been referred for prenatal evaluation. Setting-Two university hospitals. Patients-Nine patients with prolonged QT interval in the neonatal period who had been referred for prenatal evaluation. Fetal echocardiograms were obtained from 24 to 40 weeks of gestation. Indications were fetal bradycardia (five patients), a family history of long QT syndrome (two patients), and complex arrhythmias (two patients). Results-Seven fetuses had persistent sinus bradycardia without ventricular arrhythmias (heart rates 70-120 beats/ min). Five patients were treated with propranolol, after the diagnosis had been established by postnatal electrocardiogram (ECG). One of these patients died suddenly at the age of 3 weeks, after the treatment had been stopped because of profound bradycardia. One of the remaining two patients who did not receive propranolol had a syncope at the age of 6 weeks. Two fetuses presented with frequent runs of ventricular tachycardia and intermittent bradycardia caused by intermittent, functional second degree atrioventricular block. Both patients died on the first day of life despite treatment with propranolol and transvenous temporary pacing. Conclusions-Sinus bradycardia in an otherwise normal fetus may be a symptom of long QT syndrome. Postnatal ECGs and a family emination are strongly recommended in these children. In fetuses with frequent runs ofventricular tachycardia and intermittent second degree atrioventricular block long QT syndrome should be suspected prenatally. These high risk patients should be delivered in centres with a paediatric cardiology unit.