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Osnabrück, Germany

Lavezzi W.A.,Office of the District 5 Medical Examiner | Capacchione J.F.,Uniformed Services University of the Health Sciences | Muldoon S.M.,Uniformed Services University of the Health Sciences | Sambuughin N.,Uniformed Services University of the Health Sciences | And 3 more authors.
Anesthesia and Analgesia | Year: 2013

A healthy 6-year-old boy developed lower extremity rigidity, trismus, and fever after playing in a splash pool. On arrival in the emergency department, he appeared to be seizing. An endotracheal tube was emergently placed using succinylcholine. Cardiac arrest followed. He could not be resuscitated. Postmortem genetic analysis found a novel RYR1 variant. Family testing revealed the same variant in his father who also had muscle contracture testing diagnostic for susceptibility to malignant hyperthermia and central core disease diagnosed histologically. Because there was no exposure to volatile anesthetics before the onset of symptoms, this is a case of "awake" malignant hyperthermia worsened by succinylcholine. Copyright © 2013 International Anesthesia Research Society. Source


Sequeiros J.,University of Porto | Seneca S.,Center for Medical Genetics | Martindale J.,Sheffield Diagnostic Genetics Service
European Journal of Human Genetics | Year: 2010

Many laboratories worldwide are offering molecular genetic testing for spinocerebellar ataxias (SCAs). This is essential for differential diagnosis and adequate genetic counselling. The European Molecular Genetics Quality Network (EMQN) started an SCA external quality assessment scheme in 2004. There was a clear need for updated laboratory guidelines. EMQN and EuroGentest organized a Best Practice (BP) meeting to discuss current practices and achieve consensus. A pre-meeting survey showed that 36 laboratories (20 countries) conducted nearly 18 000 SCA tests the year before, and identified issues to discuss. Draft guidelines were produced immediately after the meeting and discussed online for several months. The final version was endorsed by EMQN, and harmonized with guidelines from other oligonucleotide repeat disorders. We present the procedures taken to organize the survey, BP meeting, as well as drafting and approval of BP guidelines. We emphasize the most important recommendations on (1) pre-test requirements, (2) appropriate methodologies and (3) interpretation and reporting, and focus on the discussion of controversial issues not included in the final document. In addition, after an extensive review of scientific literature, and responding to recommendations made, we now produce information that we hope will facilitate the activities of diagnostic laboratories and foster quality SCA testing. For the main loci, this includes (1) a list of repeat sequences, as originally published; (2) primers in use; and (3) an evidence-based description of the normal and pathogenic repeat-size ranges, including those of reduced penetrance and those in which there is still some uncertainty. This information will be maintained and updated in http://www.scabase.eu. © 2010 Macmillan Publishers Limited All rights reserved. Source


De Brakeleer S.,Vrije Universiteit Brussel | De Greve J.,Vrije Universiteit Brussel | Loris R.,Vrije Universiteit Brussel | Janin N.,CHU de Liege | And 3 more authors.
Human Mutation | Year: 2010

Fifteen years ago BRCA1 and BRCA2 were reported as high penetrant breast cancer predisposing genes. However, mutations in these genes are found in only a fraction of high risk families. BARD1 is a candidate breast cancer gene, but only a limited number of missense mutations with rather unclear pathogenic consequences have been reported. We screened 196 high risk breast cancer families for the occurrence of BARD1 variants. All genetic variants were analyzed using clinical information as well as IN SILICO predictive tools, including protein modeling. We found three candidate pathogenic mutations in seven families including a first case of a protein truncating mutation (p.Glu652fs) removing the entire second BRCT domain of BARD1. In conclusion, we provide evidence for an increased breast cancer risk associated to specific BARD1 germline mutations. However, these BARD1 mutations occur in a minority of hereditary breast cancer families. ©2010 Wiley-Liss, Inc. Source


Belva F.,Center for Medical Genetics | Roelants M.,Vrije Universiteit Brussel | De Schepper J.,UZ Brussel | Roseboom T.J.,Clinical Epidemiology and Biostatistics | And 3 more authors.
Human Reproduction | Year: 2012

STUDY QUESTIONDo young adolescents conceived by ICSI display a higher blood pressure than spontaneously conceived (SC) adolescents? SUMMARY ANSWERIn our study, 14-year-old male and female ICSI teenagers were not found to have increased blood pressure at rest. WHAT IS KNOWN AND WHAT THIS PAPER ADDSOnly limited data are available regarding the cardiovascular risk of children born after assisted conception and up till now, no data on the cardiovascular health in pubertal children conceived by ICSI have been published. In this study, resting blood pressure and blood pressure response to a psychological stressor were measured in a cohort of 14-year-old teenagers conceived by ICSI and compared the results with those of a group of SC peers. DESIGNIn this cross-sectional study, resting blood pressure measurements were available from 217 singleton ICSI children (116 boys, 101 girls) and 223 singleton control children born after spontaneous conception (115 boys, 108 girls). Continuous blood pressure measurements, performed during a psychological stress test, were available for only 67 ICSI and 38 SC children. PARTICIPANTS AND SETTINGThe study group comprised adolescents conceived by ICSI predominantly because of male factor infertility and they were part of a previously published cohort followed since birth; controls were a cross-sectional sample of peers born to fertile parents and recruited from comparable schools as those attended by the ICSI teenagers. Response rates were 56 (tested/reached) in the ICSI group and 50 (agreed/eligible) in the SC group, but information regarding health could be obtained in 63 and 72 of the ICSI and SC children, respectively. MAIN RESULTS AND THE ROLE OF CHANCEICSI girls had a comparable resting systolic (109 ± 9 mmHg) and diastolic (64 ± 6 mmHg) blood pressure in comparison with girls in the SC group (111 ± 9 mmHg, P=0.2 and 66 ± 7 mmHg, P=0.05), even after adjustment for age and height. After adjustment for current body characteristics, early life and parental BACKGROUNDBACKGROUND factors, systolic and diastolic blood pressure remained comparable in both groups. In ICSI boys, a slightly lower systolic (113 ± 10 mmHg), but comparable diastolic (64 ± 6 mmHg) resting blood pressure was found in comparison with the SC group (116 ± 9 mmHg; P=0.04 and 65 ± 5 mmHg; P=0.1). After adjustment for height and age, systolic and diastolic blood pressure were comparable in both groups (P=0.7 and P=0.6). After correction for current body characteristics, early life and parental factors, ICSI and SC boys still had comparable systolic (difference in ICSI versus SC:-1.1 mmHg; 95 CI:-3.81.6; P=0.4) and diastolic (difference in ICSI versus SC:-1.2 mmHg; 95 CI:-3.20.7; P=0.2) blood pressure measurements. In the small subsample of girls and boys with continuous blood pressure readings, the systolic and diastolic blood pressure response to the stress test was not significantly different between the ICSI and SC groups even after taking into account the baseline values. BIAS, CONFOUNDING AND OTHER REASONS FOR CAUTIONDespite the rather low response rate in the ICSI group and the fact that no information on current health status could be obtained from more than a quarter of the eligible comparison group, the non-participating analysis in the ICSI as well in the SC group did not reveal differences between participating and non-participating children regarding clinical characteristics. The negative results for the sub-analysis on blood pressure response to stress should be interpreted with caution, because these data were available for only a small number of children, and the analysis may be underpowered. This result can only rule out a large effect on blood pressure responsiveness to a psychological stressor. Although our sample size appears to be appropriate, our results need confirmation by others and in larger cohorts when more data become available. GENERALIZABILITY TO OTHER POPULATIONSOur results are the first described ever in ICSI offspring, born to parents suffering from predominantly male factor infertility. STUDY FUNDING/COMPETING INTEREST(S)This study was supported by research grants from Fonds voor Wetenschappelijk Onderzoek Vlaanderen, Onderzoeksraad Vrije Universiteit Brussel and Wetenschappelijk Fonds Willy Gepts. Unconditional grants from MSD Belgium, Merck International, IBSA Institut Biochimique and Ferring International Center are kindly acknowledged. © 2012 The Author. Source


Belva F.,Center for Medical Genetics | Painter R.,AMC | Bonduelle M.,Center for Medical Genetics | Roelants M.,Vrije Universiteit Brussel | And 2 more authors.
Human Reproduction | Year: 2012

BACKGROUND: Puberty is a critical period for the development of cardio-metabolic disturbances, including a more central body fat distribution. It is still unclear if IVF and more specifically ICSI, can permanently and detrimentally affect body fat accumulation in the human offspring. Therefore, adiposity and body fat distribution in 14-year-old adolescents born after ICSI were investigated. METHODS: Body composition data, including anthropometry (weight, height and BMI), skinfold thicknesses (peripheral: triceps and biceps skinfolds; central: supra-iliacal and subscapular skinfolds; total: sum of the four skinfolds) and circumferences (waist, mid-upper arm) were compared between 217 ICSI singletons (116 boys, 101 girls) and 223 singletons (115 boys, 108 girls) born after spontaneous conception (SC). ICSI teenagers were part of a previously published ICSI cohort followed since birth; SC controls were recruited from schools in the surroundings. RESULTS: Among all boys, no differences in body composition measurements were found between the ICSI and SC group, taking into account confounding variables. In boys with more advanced pubertal stages, a significantly higher sum of peripheral skinfolds was found in the ICSI group compared with the SC group (difference 3.5 mm, 95 confidence interval 0.36.6). In girls, peripheral adiposity assessed by skinfolds and mid-upper arm circumference, and central adiposity assessed by skinfolds and waist circumference as well as total adiposity assessed by BMI, the sum of four skinfold thicknesses and skinfold-derived body fat percentage were significantly higher in the ICSI group compared with the SC group, taking into account confounding variables (all P< 0.05). Neither parental nor early life factors could explain the differences. CONCLUSIONS: We found that pubertal ICSI girls were more prone to central, peripheral and total adiposity compared with their SC counterparts. ICSI adolescents with advanced pubertal stages showed more peripheral adiposity. Continued monitoring of body fat patterns in adolescents born after fertility treatment is mandatory in order to assess their risk for developing obesity and its related adverse health effects in adulthood. © The Author 2011. Source

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