TY  - JOUR
AU  - Boeschoten, M.A.
AU  - Aa, N. van der
AU  - Bakker, A.
AU  - Heide, F.J.J. ter
AU  - Hoofwijk, M.C.
AU  - Jongedijk, R.A.
AU  - Minnen, A. van
AU  - Elzinga, B.M.
AU  - Olff, M.
PY  - 2018
UR  - http://hdl.handle.net/2066/198351
AB  - Background: In 2013, the Clinician-Administered PTSD Scale, the golden standard to assess PTSD, was adapted to the DSM-5 (CAPS-5). Objective: This project aimed to develop a clinically relevant Dutch translation of the CAPS-5 and to investigate its psychometric properties. Method: We conducted a stepped translation including Delphi rounds with a crowd of 44 Dutch psychotrauma experts and five senior psychotrauma experts. Using partial crowd-translations, two professional translations and the official Dutch translation of the DSM-5, each senior expert aggregated one independent translation. Consensus was reached plenary. After back-translation, comparison with the original CAPS-5 and field testing, a last round with the senior experts resulted in the final version. After implementation clinicians conducted CAPS-5 interviews with 669 trauma-exposed individuals referred for specialized diagnostic assessment. Reliability of the Dutch CAPS-5 was investigated through internal consistency and interrater reliability analyses, and construct validity through confirmatory factor analysis (CFA). Results: CAPS-5 total severity score showed high internal consistency (alpha = .90) and interrater reliability (ICC = .98, 95% CI: .94-.99). CAPS-5 diagnosis showed modest interrater reliability (kappa = .59, 95% CI: .20-.98). CFA with alternative PTSD models revealed adequate support for the DSM-5 four-factor model, but a six-factor (Anhedonia) model fit the data best. Conclusions: The Dutch CAPS-5 is a carefully translated instrument with adequate psychometric properties. Current results add to the growing support for more refined (six and seven) factor models for DSM-5 PTSD indicating that the validity and clinical implications of these models should be objective of further research.
TI  - Development and evaluation of the Dutch Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)
SN  - 2000-8066
IS  - iss. 1
JF  - European Journal of Psychotraumatology
VL  - vol. 9
PS  - 14 p.
DO  - https://doi.org/10.1080/20008198.2018.1546085
L1  - https://repository.ubn.ru.nl/bitstream/handle/2066/198351/198351.pdf?sequence=1
ER  - 
TY  - JOUR
AU  - Ee, E. van
AU  - Jongmans, M.J.
AU  - Aa, N. van der
AU  - Kleber, R.J.
PY  - 2018
UR  - http://hdl.handle.net/2066/199138
TI  - Hechtingsrepresentaties en sensitiviteit: De modererende rol van posttraumatische stressstoornis bij een steekproef onder vluchtelingen
EP  - 363
SN  - 1566-0206
IS  - iss. 3
SP  - 349
JF  - Gezinstherapie Wereldwijd
VL  - vol. 29
PS  - 15 p.
ER  - 
TY  - JOUR
AU  - Ee, E. van
AU  - Jongmans, M.J.
AU  - Aa, N. van der
AU  - Kleber, R.J.
PY  - 2017
UR  - http://hdl.handle.net/2066/199183
AB  - It has been hypothesized that adult attachment representations guide caregiving behavior and influence parental sensitivity, and thus affect the child's socio-emotional development. Several studies have shown a link between posttraumatic stress disorder (PTSD) and reduced parental sensitivity, so it is possible that PTSD moderates the relationship between insecure attachment representations and insensitivity. In this study symptoms of PTSD (Harvard Trauma Questionnaire), parental sensitivity (Emotional Availability Scales), and attachment representations (Attachment Script Assessment) were assessed in 53 parents who were asylum seekers or refugees. Results showed that when parents were less able to draw on secure attachment representations, symptoms of PTSD increased the risk of insensitive parenting. These findings suggest that parental sensitivity is affected not just by attachment representations, but by a conjunction of risk factors including symptoms of PTSD and insecure attachment representations. These parents should therefore be supported to establish or confirm secure models of attachment experiences, to facilitate their ability interact sensitively and form a secure relationship with their children.
TI  - Attachment representation and sensitivity: The moderating role of posttraumatic stress disorder in a refugee sample
EP  - 792
SN  - 0014-7370
IS  - iss. 3
SP  - 781
JF  - Family Process
VL  - vol. 56
PS  - 12 p.
DO  - https://doi.org/10.1111/famp.12228
ER  - 
TY  - JOUR
AU  - Schuurs-Hoeijmakers, J.H.M.
AU  - Landsverk, M.L.
AU  - Foulds, N.
AU  - Kukolich, M.K.
AU  - Gavrilova, R.H.
AU  - Greville-Heygate, S.
AU  - Hanson-Kahn, A.
AU  - Bernstein, J.A.
AU  - Glass, J.
AU  - Chitayat, D.
AU  - Burrow, T.A.
AU  - Husami, A.
AU  - Collins, K.
AU  - Wusik, K.
AU  - Aa, N. van der
AU  - Kooy, F.
AU  - Brown, K.T.
AU  - Gadzicki, D.
AU  - Kini, U.
AU  - Alvarez, S.
AU  - Fernandez-Jaen, A.
AU  - McGehee, F.
AU  - Selby, K.
AU  - Tarailo-Graovac, M.
AU  - Allen, M.
AU  - Karnebeek, C.D. van
AU  - Stavropoulos, D.J.
AU  - Marshall, C.R.
AU  - Merico, D.
AU  - Gregor, A.
AU  - Zweier, C.
AU  - Hopkin, R.J.
AU  - Chu, Y.W.
AU  - Chung, B.H.
AU  - Vries, B. de
AU  - Devriendt, K.
AU  - Hurles, M.E.
AU  - Brunner, H.G.
PY  - 2016
UR  - http://hdl.handle.net/2066/167655
AB  - We report on 19 individuals with a recurrent de novo c.607C>T mutation in PACS1. This specific mutation gives rise to a recognizable intellectual disability syndrome. There is a distinctive facial appearance (19/19), characterized by full and arched eyebrows, hypertelorism with downslanting palpebral fissures, long eye lashes, ptosis, low set and simple ears, bulbous nasal tip, wide mouth with downturned corners and a thin upper lip with an unusual "wavy" profile, flat philtrum, and diastema of the teeth. Intellectual disability, ranging from mild to moderate, was present in all. Hypotonia is common in infancy (8/19). Seizures are frequent (12/19) and respond well to anticonvulsive medication. Structural malformations are common, including heart (10/19), brain (12/16), eye (10/19), kidney (3/19), and cryptorchidism (6/12 males). Feeding dysfunction is presenting in infancy with failure to thrive (5/19), gastroesophageal reflux (6/19), and gastrostomy tube placement (4/19). There is persistence of oral motor dysfunction. We provide suggestions for clinical work-up and management and hope that the present study will facilitate clinical recognition of further cases.
TI  - Clinical delineation of the PACS1-related syndrome--Report on 19 patients
EP  - 675
SN  - 1552-4825
IS  - iss. 3
SP  - 670
JF  - American Journal of Medical Genetics. Part A
VL  - vol. 170
DO  - https://doi.org/10.1002/ajmg.a.37476
ER  - 
TY  - JOUR
AU  - Smets, K.
AU  - Duarri, A.
AU  - Deconinck, T.
AU  - Ceulemans, B.
AU  - Warrenburg, B.P.C. van de
AU  - Zuchner, S.
AU  - Gonzalez, M.A.
AU  - Schule, R.
AU  - Synofzik, M.
AU  - Aa, N. van der
AU  - Jonghe, P. De
AU  - Verbeek, D.S.
AU  - Baets, J.
PY  - 2015
UR  - http://hdl.handle.net/2066/155287
AB  - BACKGROUND: Identification of the first de novo mutation in potassium voltage-gated channel, shal-related subfamily, member 3 (KCND3) in a patient with complex early onset cerebellar ataxia in order to expand the genetic and phenotypic spectrum. METHODS: Whole exome sequencing in a cerebellar ataxia patient and subsequent immunocytochemistry, immunoblotting and patch clamp assays of the channel were performed. RESULTS: A de novo KCND3 mutation (c.877_885dupCGCGTCTTC; p.Arg293_Phe295dup) was found duplicating the RVF motif and thereby adding an extra positive charge to voltage-gated potassium 4.3 (Kv4.3) in the voltage-sensor domain causing a severe shift of the voltage-dependence gating to more depolarized voltages. The patient displayed a severe phenotype with early onset cerebellar ataxia complicated by intellectual disability, epilepsy, attention deficit hyperactivity disorder, strabismus, oral apraxia and joint hyperlaxity. CONCLUSIONS: We identified a de novo KCND3 mutation causing the most marked change in Kv4.3's channel properties reported so far, which correlated with a severe and unique spinocerebellar ataxia (SCA) type 19/22 disease phenotype.
TI  - First de novo KCND3 mutation causes severe Kv4.3 channel dysfunction leading to early onset cerebellar ataxia, intellectual disability, oral apraxia and epilepsy
SN  - 1471-2350
SP  - 51
JF  - BMC Medical Genetics
VL  - vol. 16
DO  - https://doi.org/10.1186/s12881-015-0200-3
L1  - https://repository.ubn.ru.nl/bitstream/handle/2066/155287/155287.pdf?sequence=1
ER  - 
TY  - JOUR
AU  - Beunders, G.
AU  - Munnik, S.A. de
AU  - Aa, N. van der
AU  - Ceulemans, B.
AU  - Voorhoeve, E.
AU  - Groffen, A.J.
AU  - Nillesen, W.M.
AU  - Meijers-Heijboer, E.J.
AU  - Kooy, R.F.
AU  - Yntema, H.G.
AU  - Sistermans, E.A.
PY  - 2015
UR  - http://hdl.handle.net/2066/154362
AB  - AUTS2 syndrome is characterized by low birth weight, feeding difficulties, intellectual disability, microcephaly and mild dysmorphic features. All affected individuals thus far were caused by chromosomal rearrangements, variants at the base pair level disrupting AUTS2 have not yet been described. Here we present the full clinical description of two affected men with intragenic AUTS2 variants (one two-base pair deletion in exon 7 and one deletion of exon 6). Both variants are de novo and are predicted to cause a frameshift of the full-length transcript but are unlikely to affect the shorter 3' transcript starting in exon 9. The similarities between the phenotypes of both men are striking and further support that AUTS2 syndrome is a single gene disorder.
TI  - Two male adults with pathogenic AUTS2 variants, including a two-base pair deletion, further delineate the AUTS2 syndrome
EP  - 807
SN  - 1018-4813
IS  - iss. 6
SP  - 803
JF  - European Journal of Human Genetics
VL  - vol. 23
DO  - https://doi.org/10.1038/ejhg.2014.173
ER  - 
TY  - JOUR
AU  - Vandeweyer, G.
AU  - Helsmoortel, C.
AU  - Dijck, A. Van
AU  - Silfhout, A.T. van
AU  - Coe, B.P.
AU  - Bernier, R.
AU  - Gerdts, J.
AU  - Rooms, L.
AU  - Ende, J. van den
AU  - Bakshi, M.
AU  - Wilson, M.
AU  - Nordgren, A.
AU  - Hendon, L.G.
AU  - Abdulrahman, O.A.
AU  - Romano, C
AU  - Vries, B. de
AU  - Kleefstra, T.
AU  - Eichler, E.E.
AU  - Aa, N. van der
AU  - Kooy, R.F.
PY  - 2014
UR  - http://hdl.handle.net/2066/137084
TI  - The transcriptional regulator ADNP links the BAF (SWI/SNF) complexes with autism.
EP  - 326
SN  - 1552-4868
IS  - iss. 3
SP  - 315
JF  - American Journal of Medical Genetics Part C : Seminars in Medical Genetics
VL  - vol. 166
DO  - https://doi.org/10.1002/ajmg.c.31413
ER  - 
TY  - JOUR
AU  - Helsmoortel, C.
AU  - Silfhout, A.T. van
AU  - Coe, B.P.
AU  - Vandeweyer, G.
AU  - Rooms, L.
AU  - Ende, J. van den
AU  - Schuurs-Hoeijmakers, J.H.M.
AU  - Marcelis, C.L.M.
AU  - Willemsen, M.H.
AU  - Vissers, L.E.L.M.
AU  - Yntema, H.G.
AU  - Bakshi, M.
AU  - Wilson, M.
AU  - Witherspoon, K.T.
AU  - Malmgren, H.
AU  - Nordgren, A.
AU  - Anneren, G.
AU  - Fichera, M.
AU  - Bosco, P.
AU  - Romano, C
AU  - Vries, L.B.A. de
AU  - Kleefstra, T.
AU  - Kooy, R.F.
AU  - Eichler, E.E.
AU  - Aa, N. van der
PY  - 2014
UR  - http://hdl.handle.net/2066/137247
AB  - Despite the high heritability of autism spectrum disorders (ASD), characterized by persistent deficits in social communication and interaction and restricted, repetitive patterns of behavior, interests or activities, a genetic diagnosis can be established in only a minority of patients. Known genetic causes include chromosomal aberrations, such as the duplication of the 15q11-13 region, and monogenic causes, as in Rett and fragile-X syndromes. The genetic heterogeneity within ASD is striking, with even the most frequent causes responsible for only 1% of cases at the most. Even with the recent developments in next-generation sequencing, for the large majority of cases no molecular diagnosis can be established. Here, we report ten patients with ASD and other shared clinical characteristics, including intellectual disability and facial dysmorphisms caused by a mutation in ADNP, a transcription factor involved in the SWI/SNF remodeling complex. We estimate this gene to be mutated in at least 0.17% of ASD cases, making it one of the most frequent ASD-associated genes known to date.
TI  - A SWI/SNF-related autism syndrome caused by de novo mutations in ADNP
EP  - 384
SN  - 1061-4036
IS  - iss. 4
SP  - 380
JF  - Nature Genetics
VL  - vol. 46
DO  - https://doi.org/10.1038/ng.2899
ER  - 
TY  - JOUR
AU  - Iqbal, Z.
AU  - Vandeweyer, G.
AU  - Voet, M. van der
AU  - Waryah, A.M.
AU  - Zahoor, M.Y.
AU  - Besseling, J.A.
AU  - Roca, L.T.
AU  - Silfhout, A.T. van
AU  - Nijhof, B.
AU  - Kramer, J.M.
AU  - Aa, N. van der
AU  - Ansar, M.
AU  - Peeters, H.
AU  - Helsmoortel, C.
AU  - Gilissen, C.F.H.A.
AU  - Vissers, L.E.L.M.
AU  - Veltman, J.A.
AU  - Brouwer, A.P.M. de
AU  - Kooy, R. van
AU  - Riazuddin, S.
AU  - Schenck, A.
AU  - Bokhoven, H. van
AU  - Rooms, L.
PY  - 2013
UR  - http://hdl.handle.net/2066/118541
AB  - AnkyrinG, encoded by the ANK3 gene, is involved in neuronal development and signaling. It has previously been implicated in bipolar disorder and schizophrenia by association studies. Most recently, de novo missense mutations in this gene were identified in autistic patients. However, the causative nature of these mutations remained controversial. Here, we report inactivating mutations in the Ankyrin 3 (ANK3) gene in patients with severe cognitive deficits. In a patient with a borderline intelligence, severe attention deficit hyperactivity disorder (ADHD), autism and sleeping problems, all isoforms of the ANK3 gene, were disrupted by a balanced translocation. Furthermore, in a consanguineous family with moderate intellectual disability (ID), an ADHD-like phenotype and behavioral problems, we identified a homozygous truncating frameshift mutation in the longest isoform of the same gene, which represents the first reported familial mutation in the ANK3 gene. The causality of ANK3 mutations in the two families and the role of the gene in cognitive function were supported by memory defects in a Drosophila knockdown model. Thus we demonstrated that ANK3 plays a role in intellectual functioning. In addition, our findings support the suggested association of ANK3 with various neuropsychiatric disorders and illustrate the genetic and molecular relation between a wide range of neurodevelopmental disorders.
TI  - Homozygous and heterozygous disruptions of ANK3: at the crossroads of neurodevelopmental and psychiatric disorders
EP  - 1970
SN  - 0964-6906
IS  - iss. 10
SP  - 1960
JF  - Human Molecular Genetics
VL  - vol. 22
DO  - https://doi.org/10.1093/hmg/ddt043
ER  - 
TY  - JOUR
AU  - Goubau, C.
AU  - Devriendt, K.
AU  - Aa, N. van der
AU  - Crepel, A.
AU  - Wieczorek, D.
AU  - Kleefstra, T.
AU  - Willemsen, M.H.
AU  - Rauch, A.
AU  - Tzschach, A.
AU  - Ravel, T. de
AU  - Leemans, P.
AU  - Geet, C. Van
AU  - Buyse, G.
AU  - Freson, K.
PY  - 2013
UR  - http://hdl.handle.net/2066/125776
AB  - The Forkhead box G1 (FOXG1) gene encodes a transcriptional repressor essential for early development of the telencephalon. Intragenic mutations and gene deletions leading to haploinsufficiency cause the congenital variant of Rett syndrome. We here describe Rett syndrome-like patients, three of them carrying a balanced translocation with breakpoint in the chromosome 14q12 region, and one patient having a 14q12 microdeletion excluding the FOXG1 gene. The hypothesis of long-range FOXG1-regulatory elements in this region was supported by our finding of reduced FOXG1 mRNA and protein levels in platelets and skin fibroblasts from these cases. Given that FOXG1 is not only expressed in brain but also in platelets, we have studied platelet morphology in these patients and two additional patients with FOXG1 mutations. Electron microscopy of their platelets showed some enlarged, rounder platelets with often abnormal alpha, and fewer dense granules. Platelet function studies were possible in one 14q12 translocation patient with a prolonged Ivy bleeding time and a patient with a heterozygous FOXG1 c.1248C>G mutation (p.Tyr416X). Both have a prolonged PFA-100 occlusion time with collagen and epinephrine and reduced aggregation responses to low dose of ADP and epinephrine. Dense granule ATP secretion was normal for strong agonists but absent for epinephrine. In conclusion, our study shows that by using platelets functional evidence of cis-regulatory elements in the 14q12 region result in reduced FOXG1 levels in patients' platelets having translocations or deletions in that region. These platelet functional abnormalities deserve further investigation regarding a non-transcriptional regulatory role for FOXG1 in these anucleated cells.
TI  - Platelet defects in congenital variant of Rett syndrome patients with FOXG1 mutations or reduced expression due to a position effect at 14q12
EP  - 1355
SN  - 1018-4813
IS  - iss. 12
SP  - 1349
JF  - European Journal of Human Genetics
VL  - vol. 21
DO  - https://doi.org/10.1038/ejhg.2013.86
ER  - 
TY  - JOUR
AU  - Vandeweyer, G.
AU  - Aa, N. van der
AU  - Ceulemans, B.
AU  - Bon, B.W.M. van
AU  - Rooms, L.
AU  - Kooy, R.F.
PY  - 2012
UR  - http://hdl.handle.net/2066/110552
AB  - In a male patient with West Syndrome we identified a perfectly balanced, de novo balanced translocation 46,XY,t(2;6)(p15;p22.3). No known protein coding genes were disrupted by the translocation and positional effects on nearby genes were excluded by expression studies. A putative long non-coding RNA, BX118339, spans the breakpoint on chromosome 6. It can be hypothesized that disruption of this non-coding transcript plays a role in the pathogenesis of the patient.
TI  - A de novo balanced t(2;6)(p15;p22.3) in a patient with West Syndrome disrupts a lnc-RNA.
EP  - 349
SN  - 0920-1211
IS  - iss. 3
SP  - 346
JF  - Epilepsy Research
VL  - vol. 99
N1  - 1 mei 2012
DO  - https://doi.org/10.1016/j.eplepsyres.2011.12.009
ER  - 
TY  - JOUR
AU  - Bruno, D.L.
AU  - Anderlid, B.M.
AU  - Lindstrand, A.
AU  - Ravenswaaij-Arts, C.M.A. van
AU  - Ganesamoorthy, D.
AU  - Lundin, J.
AU  - Martin, C.L.
AU  - Douglas, J.
AU  - Nowak, C.
AU  - Adam, M.P.
AU  - Kooy, R.F.
AU  - Aa, N. van der
AU  - Reyniers, E.
AU  - Vandeweyer, G.
AU  - Stolte-Dijkstra, I.
AU  - Dijkhuizen, T.
AU  - Yeung, A.
AU  - Delatycki, M.
AU  - Borgstrom, B.
AU  - Thelin, L.
AU  - Cardoso, C.
AU  - Bon, B.W.M. van
AU  - Pfundt, R.
AU  - Vries, L.B.A. de
AU  - Wallin, A.
AU  - Amor, D.J.
AU  - James, P.A.
AU  - Slater, H.R.
AU  - Schoumans, J.
PY  - 2010
UR  - http://hdl.handle.net/2066/88561
AB  - BACKGROUND: Chromosome 17p13.3 contains extensive repetitive sequences and is a recognised region of genomic instability. Haploinsufficiency of PAFAH1B1 (encoding LIS1) causes either isolated lissencephaly sequence or Miller-Dieker syndrome, depending on the size of the deletion. More recently, both microdeletions and microduplications mapping to the Miller-Dieker syndrome telomeric critical region have been identified and associated with distinct but overlapping phenotypes. METHODS: Genome-wide microarray screening was performed on 7678 patients referred with unexplained learning difficulties and/or autism, with or without other congenital abnormalities. Eight and five unrelated individuals, respectively, were identified with microdeletions and microduplications in 17p13.3. RESULTS: Comparisons with six previously reported microdeletion cases identified a 258 kb critical region, encompassing six genes including CRK (encoding Crk) and YWHAE (encoding 14-3-3epsilon). Clinical features included growth retardation, facial dysmorphism and developmental delay. Notably, one individual with only subtle facial features and an interstitial deletion involving CRK but not YWHAE suggested that a genomic region spanning 109 kb, encompassing two genes (TUSC5 and YWHAE), is responsible for the main facial dysmorphism phenotype. Only the microduplication phenotype included autism. The microduplication minimal region of overlap for the new and previously reported cases spans 72 kb encompassing a single gene, YWHAE. These genomic rearrangements were not associated with low-copy repeats and are probably due to diverse molecular mechanisms. CONCLUSIONS: The authors further characterise the 17p13.3 microdeletion and microduplication phenotypic spectrum and describe a smaller critical genomic region allowing identification of candidate genes for the distinctive facial dysmorphism (microdeletions) and autism (microduplications) manifestations.
TI  - Further molecular and clinical delineation of co-locating 17p13.3 microdeletions and microduplications that show distinctive phenotypes.
EP  - 311
SN  - 0022-2593
IS  - iss. 5
SP  - 299
JF  - Journal of Medical Genetics
VL  - vol. 47
N1  - 1 mei 2010
DO  - https://doi.org/10.1136/jmg.2009.069906
ER  -