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31.
Arjan PM de Brouwer Sander B Nabuurs Ingrid EC Verhaart Astrid R Oudakker Roel Hordijk Helger G Yntema Jannet M Hordijk-Hos Krysta Voesenek Bert BA de Vries Ton van Essen Wei Chen Hao Hu Jamel Chelly Johan T den Dunnen Vera M Kalscheuer Annemieke M Aartsma-Rus Ben CJ Hamel Hans van Bokhoven Tjitske Kleefstra 《European journal of human genetics : EJHG》2014,22(4):480-485
We have identified a deletion of 3 base pairs in the dystrophin gene (DMD), c.9711_9713del, in a family with nonspecific X-linked intellectual disability (ID) by sequencing of the exons of 86 known X-linked ID genes. This in-frame deletion results in the deletion of a single-amino-acid residue, Leu3238, in the brain-specific isoform Dp71 of dystrophin. Linkage analysis supported causality as the mutation was present in the 7.6 cM linkage interval on Xp22.11–Xp21.1 with a maximum positive LOD score of 2.41 (MRX85 locus). Molecular modeling predicts that the p.(Leu3238del) deletion results in the destabilization of the C-terminal domain of dystrophin and hence reduces the ability to interact with β-dystroglycan. Correspondingly, Dp71 protein levels in lymphoblastoid cells from the index patient are 6.7-fold lower than those in control cell lines (P=0.08). Subsequent determination of the creatine kinase levels in blood of the index patient showed a mild but significant elevation in serum creatine kinase, which is in line with impaired dystrophin function. In conclusion, we have identified the first DMD mutation in Dp71 that results in ID without muscular dystrophy. 相似文献
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Bram Jacobs Tjemme Beems Ton M. van der Vliet Arie B. van Vugt Cornelia Hoedemaekers Janneke Horn Gaby Franschman Ian Haitsma Joukje van der Naalt Teuntje M. J. C. Andriessen George F. Borm Pieter E. Vos 《Neurocritical care》2013,19(1):79-89
Background
With this study we aimed to design validated outcome prediction models in moderate and severe traumatic brain injury (TBI) using demographic, clinical, and radiological parameters.Methods
Seven hundred consecutive moderate or severe TBI patients were included in this observational prospective cohort study. After inclusion, clinical data were collected, initial head computed tomography (CT) scans were rated, and at 6 months outcome was determined using the extended Glasgow Outcome Scale. Multivariate binary logistic regression analysis was applied to evaluate the association between potential predictors and three different outcome endpoints. The prognostic models that resulted were externally validated in a national Dutch TBI cohort.Results
In line with previous literature we identified age, pupil responses, Glasgow Coma Scale score and the occurrence of a hypotensive episode post-injury as predictors. Furthermore, several CT characteristics were associated with outcome; the aspect of the ambient cisterns being the most powerful. After external validation using Receiver Operating Characteristic (ROC) analysis our prediction models demonstrated adequate discriminative values, quantified by the area under the ROC curve, of 0.86 for death versus survival and 0.83 for unfavorable versus favorable outcome. Discriminative power was less for unfavorable outcome in survivors: 0.69.Conclusions
Outcome prediction in moderate and severe TBI might be improved using the models that were designed in this study. However, conventional demographic, clinical and CT variables proved insufficient to predict disability in surviving patients. The information that can be derived from our prediction rules is important for the selection and stratification of patients recruited into clinical TBI trials. 相似文献37.
Maarten A. Vink MD Maurits T. Dirksen MD PhD Jan G.P. Tijssen PhD Maarten J. Suttorp MD PhD Mark S. Patterson MBBS PhD Nan van Geloven MSc Alexander J. Ijsselmuiden MD PhD Ton Slagboom MD Ferdinand Kiemeneij MD PhD Gerrit J. Laarman MD PhD 《Catheterization and cardiovascular interventions》2012,79(6):870-877
Background : Although current clinical guidelines recommend the use of thrombus aspiration (TA) during primary percutaneous coronary intervention (PPCI), previous studies evaluating TA demonstrated contradictory results. The aim of this study was to evaluate long‐term clinical outcome after TA in adjunct to PPCI for acute ST‐segment myocardial infarction (STEMI), as compared with conventional treatment, with the use of paclitaxel‐eluting stents or bare‐metal stents. Methods : We analyzed data of the PASSION trial, in which 619 patients with STEMI were randomly assigned to a paclitaxel‐eluting stent or a bare‐metal stent. TA was performed in 311 patients (50.2%). Clinical endpoints at 2 years were compared between patients who received TA during PPCI with patients who underwent conventional PPCI. The primary outcome of interest was a composite of cardiac death, recurrent myocardial infarction (MI), or target‐lesion revascularization (TLR). A propensity score model was made to account for baseline differences that could have affected the probability of performing TA. Results : Complete follow‐up was available for 598 patients (96.6%). The cumulative incidence of the combined outcome measure of cardiac death, recurrent MI, or TLR was 40 (13.0%) in the TA group and 41 (13.5%) in the conventional PPCI group (HR 0.96; 95% CI 0.62–1.47; P = 0.84). Also after adjusting for propensity score, no significant difference in event rate was observed between both treatment groups. Conclusions : In this post‐hoc analysis of the PASSION trial, TA in adjunct to PPCI did not affect rates of major adverse cardiac events at 2 years follow‐up, as compared with conventional PPCI. © 2011 Wiley Periodicals, Inc. 相似文献
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Jeannette M. van der Stelt Ton G. Wempe Louis C. W. Pols 《Clinical linguistics & phonetics》2013,27(10-11):835-844
The influence of the mother tongue on vowel productions in infancy is different for deaf and hearing babies. Audio material of five hearing and five deaf infants acquiring Dutch was collected monthly from month 5–18, and at 24 months. Fifty unlabelled utterances were digitized for each recording. This study focused on developmental paths in vowel productions. The applied automated band filtering analysis is F0‐independent and results in a spectral envelope, sampled in a 40‐dimensional space. Via a Principal Component Analysis (PCA, data reduction), a vowel space for normally hearing 2‐year‐olds was constructed, enabling the projection of the individual developmental data of the infants in a two‐dimensional reference plane. Comparison of the results for the hearing and the deaf infants over 2 years indicates individual as well as group differences. The amount of hearing loss as well as the communication styles seem to be important factors in explaining differences between the infant categories. 相似文献
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