Mutations in CNNM4 Cause Jalili Syndrome, Consisting of Autosomal-Recessive Cone-Rod Dystrophy and Amelogenesis Imperfecta

The combination of recessively inherited cone-rod dystrophy (CRD) and amelogenesis imperfecta (AI) was first reported by Jalili and Smith in 1988 in a family subsequently linked to a locus on chromosome 2q11, and it has since been reported in a second small family. We have identified five further ethnically diverse families cosegregating CRD and AI. Phenotypic characterization of teeth and visual function in the published and new families reveals a consistent syndrome in all seven families, and all link or are consistent with linkage to 2q11, confirming the existence of a genetically homogenous condition that we now propose to call Jalili syndrome. Using a positional-candidate approach, we have identified mutations in the CNNM4 gene, encoding a putative metal transporter, accounting for the condition in all seven families. Nine mutations are described in all, three missense, three terminations, two large deletions, and a single base insertion. We confirmed expression of Cnnm4 in the neural retina and in ameloblasts in the developing tooth, suggesting a hitherto unknown connection between tooth biomineralization and retinal function. The identification of CNNM4 as the causative gene for Jalili syndrome, characterized by syndromic CRD with AI, has the potential to provide new insights into the roles of metal transport in visual function and biomineralization

[Multidisciplinary management of severe pre-eclampsia].

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Acute appendicitis as an unexpected cause of inverted takotsubo cardiomyopathy

Takotsubo cardiomyopathy (TTC), also known as transient left ventricular ballooning syndrome, is a stress-induced-cardiomyopathy. It is precipitated by emotional or physical stress and is characterized by normal coronary arteries and transient regional wall motion abnormalities. Variants of TTC include apical ballooning syndrome and, less commonly, mid, basal, and local variants. New onset heart failure or acute coronary syndromes are a common presentation of TTC. Arrhythmias such as VT, VF, and torsade de pointes have also been reported. We present here a 42-year-old man with an inverted Takotsubo variant with pulmonary edema and transient accelerated idioventricular rhythm. He was initially admitted in the Emergency Department for acute and non-complicated appendicitis. Coronary angiogram showed normal coronary arteries and left ventriculography revealed a reverse variant of TTC. The patient had completely recovered. Myocarditis was ruled out by cardiac magnetic resonance imaging

Impact of manual thrombectomy on myocardial reperfusion as assessed by ST-segment resolution in STEMI patients treated by primary PCI

SummaryBackgroundIn STEMI patients treated by primary PCI, damage of the microvascular circulation caused by distal embolization of thrombotic material affects the quality of myocardial reperfusion. Important controversies remain concerning the usefulness of the manual thrombectomy to improve myocardial perfusion. The aim of this study is to evaluate the impact of manual thrombectomy on ST resolution as a surrogate of reperfusion extent.MethodsTwo hundred and thirty-nine consecutive STEMI patients with an <12hours onset of symptoms, were enrolled in an observational registry. Patients were divided into two cohorts according to the reperfusion strategy: manual thrombectomy before primary PCI (n=102) or conventional-PCI (n=137). The primary endpoint was the post procedural frequency of complete (>70%) resolution of ST segment elevation.ResultsA complete resolution of ST segment elevation occurred in 51.4% of patients in the thrombectomy group and in 35,6% of those in the conventional-PCI group (P=0.018). Thrombectomy strategy was associated with a lower use of stents. Multivariate analysis identified manual thrombectomy (HR=2.08 IC 95% (1.01–4.26); P=0.046), inferior location and short ischemic delay (<180min) as independent predictors of ST resolution. The cumulative Kaplan-Meier estimate of MACE was not significantly different between the two groups at one, three years follow-up.ConclusionIn STEMI patients, manual thrombectomy improves myocardial reperfusion as assessed by the percentage of ST segment resolution and a lower use of stents. However, in this cohort of limited size, this strategy did not translate into an improved cardiovascular outcome at one year follow-up

Outcomes at 7 Years of Age of Former Very Preterm Neonates with Repeated Surfactant Treatment for Prolonged Respiratory Distress in the Neonatal Period

International audienceThis study aimed at evaluating the 7-year outcomes of 118 very preterm newborns (VPNs, gestational age = 26 ± 1.4 w) involved in a randomized controlled trial. They presented neonatal respiratory distress (RDS), requiring ventilation for 14 ± 2 days post-natal age (PNA). A repeated instillation of 200 mg/kg poractant alfa (SURF) did not improve early bronchopulmonary dysplasia, but the SURF infants needed less re-hospitalization than the controls for respiratory problems at 1- and 2-year PNA. There was no growth difference at 7.1 ± 0.3 years between 41 SURF infants and 36 controls (80% of the eligible children), and 7.9% SURF infants vs. 28.6% controls presented asthma (p = 0.021). The children underwent cognitive assessment (WISC IV) and pulmonary function testing (PFT), measuring their spirometry, lung volume, and airway resistance. The spirometry measures showed differences (p 85 in both groups. Repeated surfactant treatment in VPNs presenting severe RDS led to the attenuation of early lung injuries, with an impact on long-term pulmonary sequelae, without differences in neurodevelopmental outcomes

Late Surfactant Administration in Very Preterm Neonates With Prolonged Respiratory Distress and Pulmonary Outcome at 1 Year of Age

International audienceIMPORTANCE Although immature neonate survival has improved, there is an increased risk of developing bronchopulmonary dysplasia, leading to significant respiratory morbidity. Measures to reduce bronchopulmonary dysplasia are not always effective or have important adverse effects.OBJECTIVE To evaluate the effect of late surfactant administration in infants with prolonged respiratory distress on ventilation duration, respiratory outcome at 36 weeks' postmenstrual age, and at 1 year postnatal age.DESIGN, SETTING, AND PARTICIPANTS Double-blind randomized clinical trial at 13 level III French perinatal centers. Participants included 118 neonates at less than 33 weeks' gestation who still required mechanical ventilation on day 14 (SD, 2) with fraction of inspired oxygen of more than 0.30. All survivors were eligible for follow-up. We performed an intent-to-treat analysis. INTERVENTIONS Infants received 200 mg/kg of poractant alfa (surfactant) or air after randomization. At 1 year, after parents' interview, infants underwent physical examination by pediatricians not aware of the randomization.MAIN OUTCOMES AND MEASURES The duration of ventilation was the primary outcome. The combined outcome of death or bronchopulmonary dysplasia at 36 weeks' postmenstrual age and respiratory morbidity at 1 year of age were the main secondary outcome measures. RESULTS Of the 118 infants who participated in the study, 65 (55%) were male. Fraction of inspired oxygen requirements dropped after surfactant, but not air, for up to 24 hours after instillation (0.36 [0.11] vs 0.43 [0.18]; P < .005). Severe bronchopulmonary dysplasia/death rates at 36 weeks' postmenstrual age were similar (27.1% vs 35.6%; P = .32). Less surfactant-treated infants needed rehospitalization for respiratory problems after discharge (28.3% vs 51.1%; P = .03); 39.5% vs 50% needed respiratory physical therapy (P = .35). No difference was observed for weight (7.8 [1.2] kg vs 7.6 [1.1] kg), height (69 [5] cm vs 69 [3] cm), and head circumference (44.4 [1.7] cm vs 44.2 [1.7] cm) measured at follow-up, nor for neurodevelopment outcome. CONCLUSIONS AND RELEVANCE Late surfactant administration did not alter the early course of bronchopulmonary dysplasia. However, surfactant-treated infants had reduced respiratory morbidity prior to 1 year of age

The distribution of T-DNA in the genomes of transgenic Arabidopsis and rice

Abstract Almost all the nuclear genes of four Gramineae (maize, wheat, barley, rice) and pea are located in DNA fractions covering only a 1-2% GC range and representing between 10 and 25% of the different genomes. These DNA fractions comprise large gene-rich regions (collectively called the 'gene space') separated by vast gene-empty, repeated sequences. In contrast, in Arabidopsis thaliana, genes are distributed in DNA fractions covering an 8% GC range and representing 85% of the genome. Here, we investigated the integration of a transferred DNA (T-DNA) in the genomes of Arabidopsis and rice and found different patterns of integration, which are correlated with the different gene distributions. While T-DNA integrates essentially everywhere in the Arabidopsis genome, integration was detected only in the gene space, namely in the gene-rich, transcriptionally active, regions of the rice genome. The implications of these results for the integration of foreign DNA are discussed. (Résumé d'auteur