TY - THES A1 - Zierhut, Tanja T1 - Die Situation von Eltern mit schwer entwicklungsgestörten Kindern - Ergebnisse einer Elternbefragung T1 - The situation of parents with severly developmental disordered children– results of interviews with parents N2 - Bei der Behandlung von Kindern mit Entwicklungsauffälligkeiten ist nicht nur die medizinisch-therapeutische Versorgung der Kinder, sondern auch die Gesamtbetreuung der Familien von großer Bedeutung. Um den aktuellen Stand der Versorgung von Kindern mit Intelligenzminderung und ihren Eltern aus sozialpädiatrischer Sicht zu erfassen, wurde in Zusammenarbeit mit drei engagierten und selbst betroffenen Eltern ein Fragebogen erarbeitet. Es wurden der Stellenwert einer genauen Diagnose der Entwicklungsstörung für die Eltern, die Einschätzung der eingeleiteten Behandlungs- und Betreuungsmaßnahmen sowie der humangenetischen Möglichkeiten und die Qualität der erhaltenen Informationen untersucht. Ergänzend wurden mit 10 Eltern ausführliche, halbstrukturierte Interviews durchgeführt. N2 - Not only support of children, but also support of the respective families is of great importance while treating developmental disordered childen To obtain the current status of support for mental retarded children and their parents point of view, a questionaire has been developed in cooperation with three active and affected parents. The importance of an exact diagnosis of developmental disorder for parents, the assessment of initiated treatment, medical care and human genetic options and quality of received information was examined. In addition 10 parents were personally interviewed. KW - Humangenetik KW - behindert KW - Sozialpädiatrie KW - human genetics KW - handicapped KW - social pediatrics Y1 - 2005 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-18459 ER - TY - JOUR A1 - Harter, Philipp A1 - Hauke, Jan A1 - Heitz, Florian A1 - Reuss, Alexander A1 - Kommoss, Stefan A1 - Marmé, Frederik A1 - Heimbach, André A1 - Prieske, Katharina A1 - Richters, Lisa A1 - Burges, Alexander A1 - Neidhardt, Guido A1 - de Gregorio, Nikolaus A1 - El-Balat, Ahmed A1 - Hilpert, Felix A1 - Meier, Werner A1 - Kimmig, Rainer A1 - Kast, Karin A1 - Sehouli, Jalid A1 - Baumann, Klaus A1 - Jackisch, Christian A1 - Park-Simon, Tjoung-Won A1 - Hanker, Lars A1 - Kröber, Sandra A1 - Pfisterer, Jacobus A1 - Gevensleben, Heidrun A1 - Schnelzer, Andreas A1 - Dietrich, Dimo A1 - Neunhöffer, Tanja A1 - Krockenberger, Mathias A1 - Brucker, Sara Y. A1 - Nürnberg, Peter A1 - Thiele, Holger A1 - Altmüller, Janine A1 - Lamla, Josefin A1 - Elser, Gabriele A1 - du Bois, Andreas A1 - Hahnen, Eric A1 - Schmutzler, Rita T1 - Prevalence of deleterious germline variants in risk genes including \(BRCA1/2\) in consecutive ovarian cancer patients (AGO-TR-1) JF - PLoS ONE N2 - Background Identification of families at risk for ovarian cancer offers the opportunity to consider prophylactic surgery thus reducing ovarian cancer mortality. So far, identification of potentially affected families in Germany was solely performed via family history and numbers of affected family members with breast or ovarian cancer. However, neither the prevalence of deleterious variants in \(BRCA1/2\) in ovarian cancer in Germany nor the reliability of family history as trigger for genetic counselling has ever been evaluated. Methods Prospective counseling and germline testing of consecutive patients with primary diagnosis or with platinum-sensitive relapse of an invasive epithelial ovarian cancer. Testing included 25 candidate and established risk genes. Among these 25 genes, 16 genes (\(ATM\), \(BRCA1\), \(BRCA2\), \(CDH1\), \(CHEK2\), \(MLH1\), \(MSH2\), \(MSH6\), \(NBN\), \(PMS2\), \(PTEN\), \(PALB2\), \(RAD51C\), \(RAD51D\), \(STK11\), \(TP53\)) were defined as established cancer risk genes. A positive family history was defined as at least one relative with breast cancer or ovarian cancer or breast cancer in personal history. Results In total, we analyzed 523 patients: 281 patients with primary diagnosis of ovarian cancer and 242 patients with relapsed disease. Median age at primary diagnosis was 58 years (range 16–93) and 406 patients (77.6%) had a high-grade serous ovarian cancer. In total, 27.9% of the patients showed at least one deleterious variant in all 25 investigated genes and 26.4% in the defined 16 risk genes. Deleterious variants were most prevalent in the \(BRCA1\) (15.5%), \(BRCA2\) (5.5%), \(RAD51C\) (2.5%) and \(PALB2\) (1.1%) genes. The prevalence of deleterious variants did not differ significantly between patients at primary diagnosis and relapse. The prevalence of deleterious variants in \(BRCA1/2\) (and in all 16 risk genes) in patients <60 years was 30.2% (33.2%) versus 10.6% (18.9%) in patients \(\geq\)60 years. Family history was positive in 43% of all patients. Patients with a positive family history had a prevalence of deleterious variants of 31.6% (36.0%) versus 11.4% (17.6%) and histologic subtype of high grade serous ovarian cancer versus other showed a prevalence of deleterious variants of 23.2% (29.1%) and 10.2% (14.8%), respectively. Testing only for \(BRCA1/2\) would miss in our series more than 5% of the patients with a deleterious variant in established risk genes. Conclusions 26.4% of all patients harbor at least one deleterious variant in established risk genes. The threshold of 10% mutation rate which is accepted for reimbursement by health care providers in Germany was observed in all subgroups analyzed and neither age at primary diagnosis nor histo-type or family history sufficiently enough could identify a subgroup not eligible for genetic counselling and testing. Genetic testing should therefore be offered to every patient with invasive epithelial ovarian cancer and limiting testing to \(BRCA1/2\) seems to be not sufficient. KW - medicine KW - Genetic causes of cancer KW - ovarian cancer KW - cancer risk factors KW - histology KW - cancer detection and diagnosis KW - breast cancer KW - genetic testing KW - human genetics Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173553 VL - 12 IS - 10 ER - TY - JOUR A1 - Grassmann, Felix A1 - Fritsche, Lars G. A1 - Keilhauer, Claudia N. A1 - Heid, Iris M. A1 - Weber, Bernhard H. F. T1 - Modelling the Genetic Risk in Age-Related Macular Degeneration JF - PLoS One N2 - Late-stage age-related macular degeneration (AMD) is a common sight-threatening disease of the central retina affecting approximately 1 in 30 Caucasians. Besides age and smoking, genetic variants from several gene loci have reproducibly been associated with this condition and likely explain a large proportion of disease. Here, we developed a genetic risk score (GRS) for AMD based on 13 risk variants from eight gene loci. The model exhibited good discriminative accuracy, area-under-curve (AUC) of the receiver-operating characteristic of 0.820, which was confirmed in a cross-validation approach. Noteworthy, younger AMD patients aged below 75 had a significantly higher mean GRS (1.87, 95% CI: 1.69-2.05) than patients aged 75 and above (1.45, 95% CI: 1.36-1.54). Based on five equally sized GRS intervals, we present a risk classification with a relative AMD risk of 64.0 (95% CI: 14.11-1131.96) for individuals in the highest category (GRS 3.44-5.18, 0.5% of the general population) compared to subjects with the most common genetic background (GRS -0.05-1.70, 40.2% of general population). The highest GRS category identifies AMD patients with a sensitivity of 7.9% and a specificity of 99.9% when compared to the four lower categories. Modeling a general population around 85 years of age, 87.4% of individuals in the highest GRS category would be expected to develop AMD by that age. In contrast, only 2.2% of individuals in the two lowest GRS categories which represent almost 50% of the general population are expected to manifest AMD. Our findings underscore the large proportion of AMD cases explained by genetics particularly for younger AMD patients. The five-category risk classification could be useful for therapeutic stratification or for diagnostic testing purposes once preventive treatment is available. KW - AMD KW - complement factor-H KW - grading system KW - United States KW - vitamin C KW - prevalence KW - variants KW - susceptibility KW - association KW - maculopathy KW - variant genotypes KW - genetic loci KW - macular degeneration KW - genetics of disease KW - eyes KW - cased-control studies KW - genotyping KW - human genetics Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131315 VL - 7 IS - 5 ER -