13 research outputs found
Chikungunya Virus Infection during Pregnancy, RĂ©union, France, 2006
Except for prenatal hospital admissions for those infected, this virus had no effect on outcomes
Deletion of 5' sequences of the CSB gene provides insight into the pathophysiology of Cockayne syndrome.
Cockayne syndrome is an autosomal recessive neurodegenerative disorder characterized by a specific defect in the repair of UV-induced DNA lesions. Most cases of Cockayne syndrome are caused by mutations in the CSB gene but the pathophysiological mechanisms are poorly understood. We report the clinical and molecular data of two severely affected Cockayne patients with undetectable CSB protein and mRNA. Both patients showed severe growth failure, microcephaly, mental retardation, congenital cataracts, retinal pigmentary degeneration, photosensitivity and died at the ages of 6 and 8 years. UV irradiation assays demonstrated that both patients had the classical DNA repair defect. Genomic DNA sequencing of the CSB gene showed a homozygous deletion involving non-coding exon 1 and upstream regulatory sequences, but none of the coding exons. Functional complementation using a wild-type CSB expression plasmid fully corrected the DNA repair defect in transfected fibroblasts. Horibata et al recently proposed that all type of CSB mutations result in a defect in UV damage repair that is responsible for the photosensitivity observed in the syndrome, but that only truncated CSB polypeptides generated by nonsense mutations have some additional inhibitory functions in transcription or in oxidative damage repair, which are necessary to lead to the other features of the phenotype. Our patients do not fit the proposed paradigm and new hypotheses are required to account for the pathophysiology of Cockayne syndrome, at the crossroads between DNA repair and transcription
Is Pregnancy Outcome Influenced by Chikungunya Infection? A Case-Control Study in 1401 Pregnant Women Enrolled in the CHIMERE Cohort
International audienceBackground: In 2005â06 a Chikungunya virus outbreak infected 38% of Runion Island population. Forty-two cases of mother to child transmission were described for the first time. The purpose of the CHIMERE cohort study was to determine the consequences of Chikungunya infection on pregnancy outcomes. Methods: In 2006, 1401 pregnant women were enrolled in the CHIMERE cohort. The diagnosis of Chikungunya was based either on serology (IgM & IgG Chikungunya specific serology) planned at inclusion and at delivery, or RT-PCR performed in case of symptoms. We determined that 584 women were not infected by the virus at delivery (IgMâ and IgGâ), 648 were infected antepartum (IgM+, RT-PCR+, or IgG seroconversion) and 27 before pregnancy, date of infection was imprecise for 50 and assessment was incomplete for 92. We compared pregnancy outcome (prenatal hospitalization, fetal-loss and stillbirth, premature delivery, mode of delivery, birth weight, fetal malformations, newborn hospitalization) between the 584 women free of Chikungunya infection and the 648 infected during pregnancy. This prospective multicentric study has been approved by IRB (CPP de Tours, France). Results: For the 648 women infected by Chikungunya during pregnancy, the infection occurred during the first, second, and third trimester for 15, 59 and 26%, respectively; 50% presented fever, 94% arthralgia and 75% skin rash. The only difference between non-infected and infected women was the number of hospitalization during pregnancy (28 versus 42%, p = 0.0001). Other outcomes, fetal loss and stillbirth (2.2 versus 2.0%), premature delivery (12 versus 10%), cesarean rates (18 versus 16%), birth weight (3067 versus 3121 g), fetal malformations (5.0 versus 5.7%) and newborn hospitalization (6.7 versus 7.4%) were similar. Conclusion: We do not find any impact of Chikungunya infection on pregnancy outcomes except for the number of prenatal hospitalizations
Mutation in a primate-conserved retrotransposon reveals a noncoding RNA as a mediator of infantile encephalopathy
International audienceThe human genome is densely populated with transposons and transposon-like repetitive elements. Although the impact of these transposons and elements on human genome evolution is recognized, the significance of subtle variations in their sequence remains mostly unexplored. Here we report homozygosity mapping of an infantile neurodegenerative disease locus in a genetic isolate. Complete DNA sequencing of the 400-kb linkage locus revealed a point mutation in a primate-specific retrotransposon that was transcribed as part of a unique noncoding RNA, which was expressed in the brain. In vitro knockdown of this RNA increased neuronal apoptosis, consistent with the inappropriate dosage of this RNA in vivo and with the phenotype. Moreover, structural analysis of the sequence revealed a small RNA-like hairpin that was consistent with the putative gain of a functional site when mutated. We show here that a mutation in a unique transposable element-containing RNA is associated with lethal encephalopathy, and we suggest that RNAs that harbor evolutionarily recent repetitive elements may play important roles in human brain development
Congenital heart defects in La RĂ©union Island: a 6-year survey within a EUROCAT-affiliated congenital anomalies registry
Revised Brunet-Lezine development quotient scores related to perinatal mother-to-child Chikungunya virus infection, CHIMERE cohort, Reunion Island, 2008.
<p>DQ: development quotient. DQ scores were measured between 15.8 and 27 months of age. Developmental delay is moderate if. <sup>â </sup>85â€DQ â€70, severe if. <sup>âĄ</sup>DQ score <70.</p><p>Data are means and 95% confidence intervals. <i>P</i> values are given for Kruskal-Wallis or Fisher exact tests comparing the three groups:</p>##<p><i>P</i> value<0.01 for Fisher exact test comparing unexposed uninfected <i>versus</i> infected children:</p><p>**<i>P</i> value<0.01 for Fisher exact test comparing exposed uninfected <i>versus</i> infected children.</p
Neurocognitive outcomes related to the clinical presentation of perinatal mother-to-child Chikungunya virus infection, CHIMERE cohort, Reunion Island, 2008.
<p>DQ: development quotient. DQ scores were measured between 15.8 and 27 months of age. Developmental delay is moderate if. <sup>â </sup>85â€DQ â€70, severe if. <sup>âĄ</sup>DQ score <70.</p><p>Data are means and 95% confidence intervals. <i>P</i> values are given for Kruskal-Wallis or Fisher exact tests comparing the three groups; Mann-Whitney or Fisher exact test comparing encephalopathic <i>versus</i> non encephalopathic children:</p>##<p><i>P</i> value<0.01;</p>#<p><i>P</i> value<0.05;</p><p>Mann-Whitney or Fisher exact test comparing non encephalopathic infected <i>versus</i> uninfected children:</p><p>**<i>P</i> value<0.01;</p><p>*<i>P</i> value<0.05.</p
Study population.
<p>â : seronegative for CHIKV-specific IgM and IgG antibodies ; + : seropositive for CHIKV-specific IgG antibodies; M24: 24<sup>th</sup> month, end of follow-up ; Unexposed - Uninfected and Exposed - Uninfected children were pooled as the Uninfected group (grey lozenge) and compared with Exposed - infected children as the Infected group (white lozenge) for RBL (Revised Brunet-LĂ©zine) performance.</p
Children characteristics related to perinatal mother-to-child Chikungunya virus infection, CHIMERE cohort, Reunion Island, 2008.
<p>Data are means, standard errors, numbers and percentages. <i>P</i> values are given for Kruskal-Wallis and Fisher exact tests comparing the three groups.</p>â <p>This propensity score is derived from maternal population (see table 2 of ref. <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0002996#pntd.0002996-Fritel1" target="_blank">[12]</a>) assigning positive or negative points to rounded-value beta coefficients associated with categories of maternal origin, education, marital status, parity and body mass index;</p>âĄ<p>gestational age <37 weeks;</p>#<p><10<sup>th</sup> percentile of AUDIPOG network growth charts;</p><p>*corrected for 24 months postnatal age.</p
Two-year MRI scan features of CHIKV-related white matter injury in eight children with perinatal mother-to-child Chikungunya virus infection, CHIMERE cohort, Reunion Island, 2008.
<p>Age at neuropsychological evaluation (months); GDQ: global development quotient; HC:</p><p>*head circumference is corrected for 24 months of postnatal age;</p><p>SD: standard deviation; WM: white matter; NA: not assessed. Diffuse includes frontal plus two or more lobes; CC: <i>corpus callosum</i> ; OC: ovale centrum ; VC: ventricular crossroads.</p><p>âNAA : reduction of N-acetyl-aspartate peak indicative of white matter hypometabolism or axonal loss;</p