Neurofibromatosis type 1 (NF1) is caused by loss-of-function variants in the NF1 gene. Approximately 10% of these variants affect RNA splicing and are either missed by conventional DNA diagnostics... Show moreNeurofibromatosis type 1 (NF1) is caused by loss-of-function variants in the NF1 gene. Approximately 10% of these variants affect RNA splicing and are either missed by conventional DNA diagnostics or are misinterpreted by in silico splicing predictions. Therefore, a targeted RNAseq-based approach was designed to detect pathogenic RNA splicing and associated pathogenic DNA variants. For this method RNA was extracted from lymphocytes, followed by targeted RNAseq. Next, an in-house developed tool (QURNAs) was used to calculate the enrichment score (ERS) for each splicing event. This method was thoroughly tested using two different patient cohorts with known pathogenic splice-variants in NF1. In both cohorts all 56 normal reference transcript exon splice junctions, 24 previously described and 45 novel non-reference splicing events were detected. Additionally, all expected pathogenic splice-variants were detected. Eleven patients with NF1 symptoms were subsequently tested, three of which have a known NF1 DNA variant with a putative effect on RNA splicing. This effect could be confirmed for all 3. The other eight patients were previously without any molecular confirmation of their NF1-diagnosis. A deep-intronic pathogenic splice variant could now be identified for two of them (25%). These results suggest that targeted RNAseq can be successfully used to detect pathogenic RNA splicing variants in NF1. Show less
Verkouteren, B.J.A.; Wakkee, M.; Geel, M. van; Doorn, R. van; Winnepenninckx, V.J.; Korpershoek, E.; ... ; Mosterd, K. 2021
Background: Metastatic basal cell carcinoma (mBCC) is a very rare entity, and diagnosis can be challenging. Therapeutic options are limited, and response to targeted therapy is poor. Objective: To... Show moreBackground: Metastatic basal cell carcinoma (mBCC) is a very rare entity, and diagnosis can be challenging. Therapeutic options are limited, and response to targeted therapy is poor. Objective: To demonstrate a clonal relationship between BCCs and their metastases and to explore which hedgehog pathway-related mutations are involved in mBCC. Methods: Genetic analysis was conducted in 10 primary BCCs and their metastases. Genes relevant for BCC development were analyzed in tumor and metastasis material with small molecule molecular inversion probes (smMIPs) for PTCH1, PTCH2, SMO, SUFU, GLI2, and TP53 or with targeted next generation sequencing of the same genes and CDKN2A, CDKN2B, CIC, DAXX, DDX3X, FUBP1, NF1, NF2, PTEN, SETD2, TRAF7, and the TERT promoter. Results: In 8 of 10 patients, identical gene mutations could be demonstrated in the primary tumors and their metastases. A broad spectrum of mutations was found. Four patients had SMO mutations in their tumor or metastasis, or both. All SMO mutations found were known to cause resistance to targeted therapy with vismodegib. Limitations: In 2 patients there was insufficient qualitative DNA available for genetic analysis. Conclusions: Molecular testing can help to identify the origin of a BCC metastasis and may be of prognostic and therapeutic value. ( J Am Acad Dermatol 2021;85:1135-42.) Show less
Thakkar, N.; Geel, M. van; Malda, M.; Rippe, R.C.A.; Vedder, P.H. 2020
This study provides a systematic review of literature from India on traditional bullying and victimization among school-going adolescents. A search of bibliographic electronic databases PsycINFO,... Show moreThis study provides a systematic review of literature from India on traditional bullying and victimization among school-going adolescents. A search of bibliographic electronic databases PsycINFO, MEDLINE, ERIC, Web of Science, and PubMed was performed in May 2020. Thirty-seven studies were included in the review. For each study included, the following specifics were examined: (a) methodological characteristics, (b) prevalence estimates of bullying behavior, (c) forms of bullying, (d) risk factors, and (e) consequences of bullying. Itwas found that bullying happens in India, and some risk factors for bullying and victimization in India are typical to the Indian context. In addition, bullying in India is associated with adverse consequences for both the aggressor and the victim. Many studies on bullying from India should be interpreted cautiously because of problems with data collection processes, instrumentation, and presentation of the findings. Cross-cultural comparisons for prevalence estimates, and longitudinal studies to examine the direction of possible influence between bullying and its correlates need to be conducted, tocater to the large adolescent population of India. Show less
Goemans, A.; Buisman, R.S.M.; Geel, M. van; Vedder, P. 2020
The current study examines variants of psychopathy in a community sample of Dutch adolescents (N = 2,855, 57% male) using three dimensions of psychopathy and trait anxiety. Five subgroups were... Show moreThe current study examines variants of psychopathy in a community sample of Dutch adolescents (N = 2,855, 57% male) using three dimensions of psychopathy and trait anxiety. Five subgroups were identified, two with high levels of psychopathic traits. The first seemed consistent with primary psychopathy, high on all dimensions, with additional low levels of anxiety, whereas the second showed elevated levels of anxiety, consistent with secondary psychopathy. Two variants low on psychopathic traits were identified: a low-risk variant and an anxious variant. Further, a moderate-risk group was found, with slightly above average psychopathy traits and average levels of mental health problems. The secondary psychopathy and the anxious variant reported the most problem behaviors. Boys, younger adolescents, and non-Western immigrant youth were overrepresented in the secondary group. These findings show that in a community sample psychopathy is a heterogeneous phenomenon. Show less
Geel, M. van; Goemans, A.; Zwaanswijk, W.; Gini, G.; Vedder, P. 2018
In the current study two meta-analyses are performed on longitudinal studies on peer victimization and self-esteem. The goal of these meta-analyses was to analyze whether a low self-esteem predicts... Show moreIn the current study two meta-analyses are performed on longitudinal studies on peer victimization and self-esteem. The goal of these meta-analyses was to analyze whether a low self-esteem predicts future peer victimization, or whether peer victimization predicts future low self-esteem. The databases PsycINFO, MEDLINE, and ERIC were searched for relevant literature. Two authors independently went through the retrieved articles and found four doctoral dissertations and 14 peer reviewed articles eligible for inclusion in the meta-analysis. Articles were independently coded by two authors, with good interrater agreement. A total of 16,230 youth were included in the meta-analysis on peer victimization and self-esteem, and a total of 16,394 youth were included in the meta-analysis on self-esteem and peer victimization. Significant prospective pathways were found from peer victimization to self-esteem, and from self-esteem to peer victimization, which suggests that peer victimization and self-esteem are related in a transactional manner. Analyses suggested a negligible role of publication bias in the obtained results. Moderator analyses revealed that effect sizes were smaller for studies that used peer reports, and for studies that considered longer time-spans. The results of the current study suggest that peer victimization could have long lasting negative effects on self-esteem, but also point out that children may become victims because of low self-esteem. Show less
Goemans, A.; Geel, M. van; Wilderjans, T.F.; Ginkel, J.R. van; Vedder, P. 2018
Children in foster care are often characterized by low academic outcomes which negatively impact their later lives. School engagement may be a key element to promote their academic and educational... Show moreChildren in foster care are often characterized by low academic outcomes which negatively impact their later lives. School engagement may be a key element to promote their academic and educational outcomes. However, little is known about the development of school engagement in foster children and longitudinal studies are lacking. The current study reports the findings of a three-wave longitudinal study wherein we examined the development of school engagement and analyzed which factors were predictive of school engagement in a sample of 363 Dutch foster children (age range 5–18 years, 46.6% girls). Multilevel analyses showed that characteristics related to demographics, school functioning, foster children, and foster families predicted levels of school engagement of children in foster care. Foster children's behavioral functioning and foster parents’ positive parenting appeared to be characteristics important to consider in screening and interventions. Based on the findings we suggest that teachers and foster care professionals should collaborate to ensure that school engagement and consequently school functioning becomes part of foster children's personal development plans. Show less
The goal of this three-wave longitudinal study was to analyze foster parent stress and foster children’s internalizing and externalizing behaviors in a transactional framework. Participants in this... Show moreThe goal of this three-wave longitudinal study was to analyze foster parent stress and foster children’s internalizing and externalizing behaviors in a transactional framework. Participants in this study were 237 children in foster care in the Netherlands with, mostly, long placement durations (M = 56.86 months, SD = 49.10 months). We examined concurrent, prospective unidirectional and bidirectional relations between foster children’s behavior and foster parent stress by using cross-lagged structural equation modeling and examined whether the results were stable across different subgroups of foster children. In contrast to our hypothesis, we found no bidirectional relations. There were unidirectional prospective pathways from foster children’s internalizing and externalizing problems to foster parent stress, but no significant prospective pathways from foster parent stress to foster children’s internalizing and externalizing problems. The results were fairly stable across different subgroups of foster children. The lack of bidirectional relations was unexpected given the presence of transactional relations in biological parent-child dyads. Foster parents seem not to influence their foster children when it comes to regulating problem behavior. Therefore, the question is whether foster parents can, in more general terms, help their foster children benefit from their improved home environment. Show less
This article focuses on the variability in developmental outcomes of foster children and the implications for foster care research and practice. We first provide a brief overview of our previous... Show moreThis article focuses on the variability in developmental outcomes of foster children and the implications for foster care research and practice. We first provide a brief overview of our previous work, where we have shown by means of meta-analysis and a longitudinal study that foster children greatly vary with respect to their developmental functioning. We then discuss that it is both the heterogeneity of developmental trajectories and the lack of an accurate model for predicting foster children's development that make the screening and monitoring of foster children's development important. We provide suggestions for screening and monitoring, and discuss the Brief Assessment Checklist as an example of a specific instrument available for screening and monitoring of vulnerable children exposed to severe social adversity. We conclude our article with directions to improve foster care and research on foster care, including a discussion of the effectiveness of and foster children's susceptibility to interventions, support for foster parents and the potential of large national and international studies. Show less
