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The reduction of human use in many grassland systems across Europe has led to bush encroachment and a loss of biodiversity. Low intensity grazing systems by livestock has often been used as a cost-effective management tool to counteract this process. However, not all semi-natural grasslands are suitable for this due to large distance from human settlements or adverse environmental conditions. In this study we address the question whether natural wild large ungulates can be a useful management tool as well. In nutrient-limited systems, large herbivores can affect vegetation dynamics by redistribution of nutrients next to their direct effects on the vegetation. They can preferentially forage plant species and deposit their pellets at other locations leading to nutrient redistribution. We studied whether moose ( Alces alces ) in the Biebrza National Park (Poland), plays a role in nitrogen dynamics. Microscopic analyses of faeces showed that 57% of the diet consisted of Salix cinerea , which was preferentially foraged upon indicated by a positive Jacobs’ selectivity index. Pellet density was significantly higher in patches of S. cinerea compared to the surrounding vegetation. Based on the chemical composition of moose pellets and the pellet density, we calculated that moose-derived N (faeces and urine) leads to a relevant N-input in willow patches compared to other sources of N in the system. We show that moose do not redistribute nitrogen between different vegetation types but instead speed up the local recycling of nitrogen in patches dominated by willows during the growing season. As a consequence, nutrients become quicker available here than in other parts of the system. We hypothesize that enhanced N-availability in willow patches may off-set the growth reduction caused by moose browsing on willows, which fits to the observed continuous expansion of willows in the study area despite high density of moose. This suggests that moose likely stimulate the growth of willow rather than the often supposed suppression of this woody species. In these systems, more labour-intensive management (f.e. mowing) is required to counteract bush encroachment. [ABSTRACT FROM AUTHOR]

Children with unexplained developmental disabilities or congenital anomalies are increasingly being referred for genetic diagnostic testing using array-comparative genomic hybridisation (array- CGH) and next-generation sequencing ( NGS) technologies. Their parents will have to deal with the secondary variants that will inevitably arise. We conducted 16 prospective semi-structured interviews with native Dutch-speaking parents whose children had undergone clinical array- CGH testing. The interviews explored the parents' experiences, expectations and opinions, specifically regarding the communication of results. Concrete examples of 'unexpected results' were provided to help guide the discussion, differing in severity, treatability, time of onset, level of risk, and carrier status. Data was analysed using content and narrative analysis methodologies. Parental motivations for and against the disclosure of unexpected results cluster around four main themes: actionability; knowledge; context; and characteristics of the result. Most parents wished to know all types of results. Disclosure was framed within a holistic, contextual, family-wide view. Genetic counselling should aim to integrate explorations of the motivations of parents surrounding the disclosure of results with good clinical care. [ABSTRACT FROM AUTHOR]

BACKGROUND: Learning disabilities are one of the most consistently reported features in Velo-Cardio-Facial Syndrome (VCFS). Earlier reports on IQ in children with VCFS were, however, limited by small sample sizes and ascertainment biases. The aim of the present study was therefore to replicate these earlier findings and to investigate intellectual abilities in a large sample of children with VCFS. In addition, we aimed to identify factors that may contribute to within-syndrome variability in cognitive performance, such as the mode of inheritance of the deletion, sex, the presence of a heart defect and psychiatric morbidity. METHOD: IQ data of 103 children with VCFS (56 males, 47 females) were collected. Psychiatric diagnosis was additionally recorded. RESULTS: Children with VCFS had a mean full-scale IQ (FSIQ) of 73.48 (range: 50-109). There were no effects of sex, presence of a heart defect and psychiatric condition on intellectual profile. Inheritance of the deletion affected cognitive performance in VCFS, with children with familial deletions having significant lower FSIQ than children with a de novo deletion. CONCLUSIONS: Learning disabilities are very common in children with VCFS, although marked within syndrome variability is noted. One factor contributing to this variability seems to be the mode of inheritance of the deletion. [ABSTRACT FROM AUTHOR]

Background Learning disabilities are one of the most consistently reported features in Velo–Cardio–Facial Syndrome (VCFS). Earlier reports on IQ in children with VCFS were, however, limited by small sample sizes and ascertainment biases. The aim of the present study was therefore to replicate these earlier findings and to investigate intellectual abilities in a large sample of children with VCFS. In addition, we aimed to identify factors that may contribute to within-syndrome variability in cognitive performance, such as the mode of inheritance of the deletion, sex, the presence of a heart defect and psychiatric morbidity. Method IQ data of 103 children with VCFS (56 males, 47 females) were collected. Psychiatric diagnosis was additionally recorded. Results Children with VCFS had a mean full-scale IQ (FSIQ) of 73.48 (range: 50–109). There were no effects of sex, presence of a heart defect and psychiatric condition on intellectual profile. Inheritance of the deletion affected cognitive performance in VCFS, with children with familial deletions having significant lower FSIQ than children with a de novo deletion. Conclusions Learning disabilities are very common in children with VCFS, although marked within syndrome variability is noted. One factor contributing to this variability seems to be the mode of inheritance of the deletion. [ABSTRACT FROM AUTHOR]

Vesico-ureteral reflux (VUR) is a frequent condition, but in most instances, the precise cause is unknown. We here review the evidence of a genetic aetiology of VUR, inherited as an autosomal dominant trait, with variable expression. We discuss the possible pathogenetic relationship between VUR and other types of uropathies and possible strategies towards the identification of genes underlying VUR are presented. The isolation of the gene(s) responsible for uropathies will not only lead to a better insight into the embryology of the urological system, the pathogenesis of uropathies, but also to a renewed interest from clinicians in congenital uropathies. [ABSTRACT FROM AUTHOR]

We propose an approximation framework that unifies and generalizes a number of existing mean-field approximation methods for the susceptible-infected-susceptible (SIS) epidemic model on complex networks. We derive the framework, which we call the unified mean-field framework (UMFF), as a set of approximations of the exact Markovian SIS equations. Our main novelty is that we describe the mean-field approximations from the perspective of the isoperimetric problem, which results in bounds on the UMFF approximation error. These new bounds provide insight in the accuracy of existing mean-field methods, such as the N-intertwined mean-field approximation and heterogeneous mean-field method, which are contained by UMFF. Additionally, the isoperimetric inequality relates the UMFF approximation accuracy to the regularity notions of Szemerédi's regularity lemma. [ABSTRACT FROM AUTHOR]

Determining a set of "important" nodes in a network constitutes a basic endeavor in network science. Inspired by electrical flows in a resistor network, we propose the best conducting node j in a graph G as the minimizer of the diagonal element Q†jj of the pseudoinverse matrix Q† of the weighted Laplacian matrix of the graph G. We propose a new graph metric that complements the effective graph resistance RG and that specifies the heterogeneity of the nodal spreading capacity in a graph. Various formulas and bounds for the diagonal element Q†jj are presented. Finally, we compute the pseudoinverse matrix of the Laplacian of star, path, and cycle graphs and derive an expansion and lower bound of the effective graph resistance RG based on the complement of the graph G. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Newborn hearing screening was implemented in Flanders about fifteen years ago. The aim of this study was to determine the aetiology of hearing loss detected by the Flemish screening programme. Methods: From 1997 to 2011, 569 neonates were referred to our tertiary referral centre after failed neonatal screening with Auditory Brainstem Responses. In case hearing loss (HL) was confirmed, further diagnostic testing was launched. A retrospective chart review was performed analysing the degree of HL, risk factor and aetiology. Results: Metabolic disorders (0.5%), infectious diseases (35.8%), congenital malformations (6.1%) and genetic abnormalities (19.8%), whether or not syndromic, were retained. In 35% of the subjects no obvious aetiology could be determined in the current study. Conclusion: In contrast to the literature findings, this series shows a genetic syndromic cause in 80% of the genetic bilateral HL cases. On the other hand connexin positive diagnoses were mostly underrepresented in this study, showing the need for better screening. [Copyright &y& Elsevier]

Abstract: Genome-wide array comparative genome hybridization has become the first in line diagnostic tool in the clinical work-up of patients presenting with intellectual disability. As a result, chromosome X-copy number variations are frequently being detected in routine diagnostics. We retrospectively reviewed genome wide array-CGH data in order to determine the frequency and nature of chromosome X-copy number variations (X–CNV) in a cohort of 2222 sporadic male patients with intellectual disability (ID) referred to us for diagnosis. In this cohort, 68 males were found to have at least one X–CNV (3.1%). However, correct interpretation of causality remains a challenging task, and is essential for proper counseling, especially when the CNV is inherited. On the basis of these data, earlier experience and literature data we designed and propose an algorithm that can be used to evaluate the clinical relevance of X-CNVs detected in sporadic male ID patients. Applied to our cohort, 19 male ID patients (0.85%) were found to carry a (likely) pathogenic X–CNV. [Copyright &y& Elsevier]

We identified a male patient presenting with intellectual disability and agenesis of the corpus callosum, carrying an apparently balanced, reciprocal, de novo translocation t(6;14)(q25.3;q13.2). Breakpoint mapping, using array painting, identified 2 interesting candidate genes, ARID1B and MRPP3, disrupted in the patient. Unexpectedly, the rearrangement produced 3 in-frame reciprocal fusion transcripts that were further characterized. Formation of fusion transcripts is mainly reported in acquired malignancies and is very rarely observed in patients with intellectual disability (ID) and/or multiple congenital malformations (MCA). Additional experimental results suggest that ARID1B, a gene involved in chromatin remodeling, constitutes a good candidate for the central nervous system phenotype present in the patient. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Current neurocognitive theories of number processing [Dehaene, S., Piazza, M., Pinel, P., & Cohen, L. (2003). Three parietal circuits for number processing. Cognitive Neuropsychology, 20, 487–506] state that mathematical performance is made possible by two functionally and anatomically distinct subsystems of number processing: a verbal system located in the angular gyrus, which underlies the retrieval of arithmetic facts, and a quantity system located in the intraparietal sulcus, which subserves operations that involve semantic manipulations of quantity. According to this model, subtypes of math disability (MD) should be traceable to differential impairments in these subsystems. The present study investigated MD in children with velo-cardio-facial syndrome (VCFS) and aimed to verify which of these subsystems of number processing is impaired in these children. Eleven children with VCFS and 11 individually matched controls, selected from the same classes, completed a large battery of mathematical tests. Our data revealed that children with VCFS had preserved number reading abilities and preserved retrieval of arithmetic facts, both of which indicate that the verbal subsystem is not impaired in VCFS. By contrast, children with VCFS showed difficulties in number comparison, the execution of a calculation strategy and word problem solving, all of which involve the semantic manipulation of quantities. This provides evidence for a specific deficit in the quantity subsystem in children with VCFS, suggesting underlying abnormalities in the intraparietal sulcus. [Copyright &y& Elsevier]

3-D sequential integration requires top MOSFETs processed at a low thermal budget, which can impair the device reliability. In this paper, top junctionless (JL) devices are fabricated with a maximum processing temperature of 525 °C. The devices feature high k/metal replacement gate and low-temperature Si:P and SiGe:B 60% raised source and drain for nMOS and pMOS fabrication, respectively. Device matching, analog, and RF performance of the top tier devices are in-line with the state-of-the-art Si technology processed at high temperature (>1000 °C). JL devices operate at reduced electric field and can meet in specification reliability (10-year reliable operation at ${V}_{\textsf {G}}= {V}_{\textsf {th}}+ 0.6$ V, 125 °C), even without the use of “reliability” anneal. The top Si layer is transferred on CMOS planar bulk wafers with W metal-1 interconnects, using a SiCN to SiCN direct wafer bonding. Comparison with silicon-on-insulator devices fabricated with the same low-temperature flow shows no impact on device electrical performance from the Si layer transfer. [ABSTRACT FROM AUTHOR]

Strained Ge p-channel gate-all-around (GAA) devices with Si-passivation are demonstrated on high-density 45-nm active pitch starting from 300-mm SiGe strain relaxed buffer wafers. While single horizontal Ge nanowire (NW) devices are demonstrated, the process flow described in this paper can be adjusted to make vertically stacked horizontal Ge NWs to increase the drive per footprint. The demonstrated short-channel devices have round Ge NWs with 9-nm diameter and are the Ge GAA devices with the smallest channel and gate dimensions (LG = 40 nm) published to date. Electrostatics and off-state leakage are maintained down to the shortest gate lengths studied, showing drain-induced barrier lowering of 30 mV/V and sub20 nA/μm Ioff at VDD = -0.5 V and LG = 40 nm. The short-channel device subthreshold slope SS and performance can be further improved by use of high-pressure annealing in hydrogen, yielding the best SSLIN and SSSAT of 71 and 76 mV/dec reported so far for any LG = 40-nm Ge pMOS channel device. [ABSTRACT FROM PUBLISHER]

The evaluation of facial dysmorphism is a critical step toward reaching a diagnostic. The aim of the present study was to evaluate the ability to interpret facial morphology in African children with intellectual disability ( ID). First, 10 experienced clinicians (five from Africa and five from Europe) rated gestalt in 127 African non-Down Syndrome (non- DS) patients using either the score 2 for 'clearly dysmorphic', 0 for 'clearly non dysmorphic' or 1 for 'uncertain'. The inter-rater agreement was determined using kappa coefficient. There was only fair agreement between African and European raters ( kappa-coefficient = 0.29). Second, we applied the FDNA Face2Gene solution to assess Down Syndrome ( DS) faces. Initially, Face2Gene showed a better recognition rate for DS in Caucasian (80%) compared to African (36.8%). We trained the Face2Gene with a set of African DS and non- DS photographs. Interestingly, the recognition in African increased to 94.7%. Thus, training improved the sensitivity of Face2Gene. Our data suggest that human based evaluation is influenced by ethnic background of the evaluator. In addition, computer based evaluation indicates that the ethnic of the patient also influences the evaluation and that training may increase the detection specificity for a particular ethnic. [ABSTRACT FROM AUTHOR]

We present a newborn diagnosed with posterior amorphous corneal dystrophy (PACD). PACD is a rare disorder with partial or complete posterior lamellar corneal opacification. Genetic screening showed a deletion of chromosome 12q21.33-q22 containing the identified four small leucine-rich proteoglycans (SLRP’s) associated with this particular dystrophy. Neither parents were carrier of the deletion. To our knowledge, this is the first report of ade novomutation causing PACD. [ABSTRACT FROM AUTHOR]

Non-invasive prenatal testing ( NIPT) for fetal aneuploidy detection is increasingly being offered in the clinical setting. Whereas the majority of tests only report fetal trisomies 21, 18 and 13, genome-wide analyses have the potential to detect other fetal, as well as maternal, aneuploidies. In this review, we discuss the technical and clinical advantages and challenges associated with genome-wide cell-free fetal DNA profiling. [ABSTRACT FROM AUTHOR]

Objectives To review early clinical manifestations of Pierre Robin sequence (PRS) and their management during the first year of life in the University Hospitals Leuven. Methods Retrospective series of 48 patients with PRS born between 2001 and 2011 and treated at a tertiary referral hospital. Review of the current literature about management of respiratory and breathing difficulties in the early life of PRS patients. Results Of our cleft palate patients 15.3% presented with PRS. A syndrome was diagnosed in 14.6%, associated anomalies without a syndromic diagnosis in 56.3% and isolated PRS in 29.2% of the cases. Mortality rate directly related to PRS was 2.1%. Respiratory difficulties were observed in 83.3% and feeding difficulties in 95.6% of the patients. Respiratory problems were addressed in a conservative way in 75%, in a non-surgical invasive way in 42.5% and in a surgical way in 12.5%. A statistically significant relationship between the association of a syndrome or other anomalies, and a higher need for resuscitation and invasive treatment were found (chi-square test, p -values = 0.019 and 0.034). Feeding difficulties were managed conservatively in 91.3%, invasively in 80.4% and surgically in 15.2%. Conclusions PRS is frequently associated with other abnormalities or syndromes. Therefore routine screening for associated anomalies in neonates with PRS is recommendable. Respiratory and feeding complications are highly frequent and possibly severe, particularly in patients with associated anomalies or syndromes, and should be recognized and addressed appropriately in an early stage. There is a potential role for the nasopharyngeal airway in reducing the need for the more traditional surgical interventions for respiratory problems. [ABSTRACT FROM AUTHOR]

Background: KBG syndrome is a rare disorder characterized by intellectual disability and associated with macrodontia of the upper central incisors, specific craniofacial findings, short stature and skeletal anomalies. Genetic corroboration of a clinical diagnosis has been possible since 2011, upon identification of heterozygous mutations in or a deletion of the ANKRD11 gene. Methods: We summarized the height data of 14 adults and 18 children (age range 2-16 years) with a genetically confirmed diagnosis of KBG syndrome. Two of these children were treated with growth hormones. Results: Stature below the 3rd centile or -1.88 standard deviation score (SDS) was observed in 72% of KBG children and in 57% of KBG adults. Height below -2.50 SDS was observed in 62% of KBG children and in 36% of KBG adults. The mean SDS of height in KBG children was -2.56 and in KBG adults -2.17. Two KBG children on growth hormone therapy increased their height by 0.6 and 1 SDS within 1 year, respectively. The former also received a gonadotropin-releasing hormone agonist due to medical necessity. Conclusion: Short stature is prevalent in KBG syndrome, and spontaneous catch-up growth beyond childhood appears limited. Growth hormone intervention in short KBG children is perceived as promising. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Evidence exists for the presence of a specific facial phenotype in nonaffected first-degree relatives of persons with CL/P. An increased risk for olfactory dysfunction has also been reported in CL/P-relatives. These phenotypic features can probably be explained via the presence of CL/P-related susceptibility genes. We aimed at confirming the occurrence of these endophenotypic traits in first-degree CL/P-relatives, and we investigated the link between the facial phenotype and the smell capacity in this group. We studied the facial morphology of 88 nonaffected first-degree relatives of patients with CL/P and 33 control subjects without family history of facial clefting by 3D surface imaging and a spatially dense analysis of the images. Smell testing was performed in 30 relatives and compared with 23 control subjects. Nonaffected relatives showed midface retrusion, hypertelorism, and olfactory dysfunction, compared to controls. In addition, we show for the first time that olfactory dysfunction in relatives is correlated to a smaller upper nasal region. This might be explained by a smaller central olfactory system. The different facial morphology in the relatives with olfactory impairment as compared to the total group may be an illustration of the contribution of different genetic backgrounds to the occurrence of CL/P via different biological pathways. [ABSTRACT FROM AUTHOR]

Using exome sequencing we identify a homozygous splice site mutation in the PIGN gene in a foetus with multiple congenital anomalies including bilateral diaphragmatic hernia, cardiovascular anomalies, segmental renal dysplasia, facial dysmorphism, cleft palate, and oligodactyly. This finding expands the phenotypic spectrum associated with homozygous loss of function mutations in PIGN , and adds further support for defective GPI anchor biosynthesis as a cause of developmental abnormalities. We demonstrate that exome sequencing is a valuable approach for the identification of a genetic cause in sporadic cases of multiple congenital anomalies (MCA) due to inherited mutations. [ABSTRACT FROM AUTHOR]

Abstract: This paper reports on the integration of vertical nTunnel FETs (TFETs) with SiGe hetero-junction and analyzes the presence of trap-assisted tunneling impacting the device behavior. Temperature measurements are used to distinguish the band-to-band tunneling (BTBT) from the trap-assisted tunneling (TAT). It is shown that TAT degrades the onset characteristic and the subthreshold swing of the devices. TCAD simulations are in good agreement with experimental data for a germanium content up to 44%, when including non-local TAT model and properly tuning the model’s parameters. Simulations also suggest that boosting the BTBT component, for example by further bandgap decrease (Ge source), or by other means should be beneficial in lowering the impact of trap-assisted tunneling, provided that the material defectivity does not worsen. [Copyright &y& Elsevier]

An abstract of the conference paper "Skeletal dysplasias: does first trimester NT measurement matter?" by N. Roggen and colleagues is presented.

A letter to the editor is presented which reports the duplication or mutation in the faciogenital dysplasia 1 (FGD1) gene in Aarskog-Scott syndrome.

Abstract: This work presents a process to fabricate Bulk FinFETs with advancements in critical fabrication steps such as the shallow trench oxide recess and the adjustment of the fin height. These steps are accomplished with the adoption of Siconi™ Selective Material Removal (SMR™) in the fabrication flow. FinFETs obtained with this new integration scheme were tested in a co-fabrication process flow proposed to integrate planar CMOS and Bulk FinFETs on the same wafer. Morphological and electrical results indicate perfectly filled trenches, a better fin height control and a Bulk FinFET static performance similar to planar CMOS. The 20nm wide fins are fabricated using 193nm illumination lithography followed by a series of trimming steps during the trench etching, the filling and a fin re-oxidation during the steam densification of the trench filling oxide. Trench depth is 300nm and the electrically active fin height is 40nm. [Copyright &y& Elsevier]

Array comparative genomic hybridization (aCGH) has led to an increased detection of causal chromosomal imbalances in individuals with congenital heart defects (CHD). The introduction of aCGH as a diagnostic tool in a clinical cardiogenetic setting entails numerous challenges. Based on our own experience as well as those of others described in the literature, we outline the state of the art and attempt to answer a number of outstanding questions such as the detection frequency of causal imbalances in different patient populations, the added value of higher-resolution arrays, and the existence of predictive factors in syndromic cases. We introduce a step-by-step approach for clinical interpretation of copy number variants (CNV) detected in CHD, which is primarily based on gene content and overlap with known chromosomal syndromes, rather than on CNV inheritance and size. Based on this algorithm, we have reclassified the detected aberrations in aCGH studies for their causality for syndromic and non-syndromic CHD. From this literature overview, supplemented with own investigations in a cohort of 46 sporadic patients with severe non-syndromic CHD, it seems clear that the frequency of causal CNVs in non-syndromic CHD populations is lower than that in syndromic CNV populations (3.6 vs. 19%). Moreover, causal CNVs in non-syndromic CHD mostly involve imbalances with a moderate effect size and reduced penetrance, whereas the majority of causal imbalances in syndromic CHD consistently affects human development and significantly reduces reproductive fitness. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Crepel A, Breckpot J, Fryns J-P, De la Marche W, Steyaert J, Devriendt K, Peeters H. DISC1 duplication in two brothers with autism and mild mental retardation. We describe the identification and delineation of an inherited 2.07 Mb microduplication in 1q42.2 in two brothers with autism and mild mental retardation. Since this duplication was not present in 1577 Belgian persons, we consider this as an extremely rare variant which has the potential to provide further insight into the genetics of autism. The duplication contains seven genes including the DISC1 gene, an interesting candidate gene that has been associated to schizophrenia, bipolar disorder, autism and Asperger syndrome. In this report we describe additional analyses undertaken to investigate the causal relationship of the duplication to the autism phenotype. We conclude that the 1q42.2 microduplication probably confers susceptibility to autism in the current family. This study is a typical illustration of the difficult interpretation of causality of a very rare variant in neuropsychiatric disease and the challenge of genetic counselling in a particular family. [ABSTRACT FROM AUTHOR]

Focal dermal hypoplasia (FDH), Goltz or Goltz–Gorlin syndrome, is an X-linked dominant multisystem disorder characterized primarily by involvement of the skin, skeletal system and eyes. We screened for mutations in the PORCN gene in eight patients of Belgian and Finnish origin with firm clinical suspicion of FDH. First, we performed quantitative PCR (qPCR) analysis to define the copy number at this locus. Next, we sequenced the coding regions and flanking intronic sequences of the PORCN gene. Three de novo mutations were identified in our patients with FDH: a 150-kb deletion removing six genes including PORCN, as defined by qPCR and X-array-CGH, and two heterozygous missense mutations; c.992T>G (p.L331R) in exon 11 and c.1094G>A (p.R365Q) in exon 13 of the gene. Both point mutations changed highly conserved amino acids and were not found in 300 control X chromosomes. The three patients in whom mutations were identified all present with characteristic dermal findings together with limb manifestations, which were not seen in our mutation-negative patients. The clinical characteristics of our patients with PORCN mutations were compared with the previously reported mutation-positive cases. In this report, we summarize the literature on PORCN mutations and associated phenotypes. [ABSTRACT FROM AUTHOR]

Abstract: Flexibly controllable threshold voltage (V th) asymmetric gate oxide thickness (T ox) independent double-gate (DG) FinFETs (4T-FinFETs) have been demonstrated. Thin drive-gate oxide (HfO2 or SiON or SiO2) and slightly thick V th-control-gate oxide (thick SiO2+drive-gate oxide) have been successfully incorporated into the 4T-FinFETs by utilizing the ion-bombardment-enhanced etching of SiO2. It was experimentally confirmed that, all the asymmetric T ox 4T-FinFETs give the significantly improved subthreshold slope and thus gain higher on-current as compared to the symmetric one. Simulation results showed that the asymmetric T ox 4T-FinFETs are advantageous even in 20-nm-gate-length region. [Copyright &y& Elsevier]

The aim of this study was to compare the motor development of primary school children (age 5-14y) with a 22q11 deletion (del22q11) group and a control group. The effects of a congenital heart defect (CHD) and IQ on motor development were additionally studied within the del22q11 group. Motor development of 37 children with a del22q11 (20 males, 17 females; mean age 9y 4mo, range 5y 9mo-13y 3mo) and 34 controls (23 males, 11 females; mean age 9y 1mo, range 4y 8mo-13y 6mo) was assessed with the Bruininks-Oseretsky Test of Motor Proficiency. The del22q11 group showed a significant deficit in motor functioning compared with the control group (p < 0.01). Within the del22q11 group there was a significant effect of IQ on motor performance, but no effect of CHD was found. To conclude, primary school children with a del22q11 syndrome showed a significant deficit in motor performance compared with a control group. A significant effect of IQ on motor performance in del22q11 was found. [ABSTRACT FROM AUTHOR]

Molecular karyotyping has revealed that microdeletions/duplications in the human genome are a major cause of multiple congenital anomalies associated with mental retardation (MCA/MR). The identification of a de novo chromosomal imbalance in a patient with MCA/MR is usually considered causal for the phenotype while a chromosomal imbalance inherited from a phenotypically normal parent is considered as a benign variation and not related to the disorder. Around 40% of imbalances in patients with MCA/MR in this series is inherited from a healthy parent and the majority of these appear to be (extremely) rare variants. As some of these contain known disease-causing genes and have also been found to be de novo in MCA/MR patients, this challenges the general view that such familial variants are innocent and of no major phenotypic consequence. Rather, we argue, that human genomes can be tolerant of genomic copy number variations depending on the genetic and environmental background and that different mechanisms play a role in determining whether these chromosomal imbalances manifest themselves. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: In this paper, we report on the integration of a spin-on low-k material (ENSEMBLE™ PMD) at the pre-metal dielectric (PMD) level of CMOS logic circuits processed using 0.13μm node modules. Modifications to the conventional integration flow, where high-density plasma phospho-silicate glass (HDP-PSG) is used as PMD material, are made to the planarization steps and etch/strip sequence. Although on stand-alone transistors there is no measurable impact of the lower capacitance, a significant decrease of the switching delay of invertors in ring oscillator structures loaded with a metal/poly plate capacitor is observed. This demonstrates the possible positive impact of low-k on the performance of circuits of which the lowest level of back-end routing has a large overlap to underlying silicided areas. [Copyright &y& Elsevier]

Constitutional Complex Chromosomal Rearrangements (CCRs) are very rare. While the vast majority of CCRs involve more than one chromosome, only seven cases describe CCRs with four or more breakpoints within a single chromosome. Here, we present a patient with multiple congenital anomalies and mental retardation. Array Comparative Genomic Hybridisation (array CGH), FISH and Multicolour Banding FISH revealed a de novo complex rearrangement with two deletions, a duplication and an inversion of 4q. This CCR involving at least seven breakpoints is one of the most complex rearrangements of a single chromosome reported thus far. Potential mechanisms generating such complex rearrangements are discussed. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Oculo-dento-digital dysplasia (ODDD) is an autosomal dominant disorder characterized by developmental anomalies of the face, the eyes, the limbs and the teeth. Patients with ODDD usually present with complete syndactyly of the fourth and fifth fingers (type III syndactyly), ocular changes, abnormalities of primary and permanent dentition and specific craniofacial malformations. Mutations in GJA1, a gene that encodes the gap junction protein connexin 43, are responsible for ODDD. Gap junctions are assemblies of intercellular channels that allow exchange of various ions and signaling molecules between cells. In this way, gap junctions play an important regulatory role in a variety of physiologic and developmental processes. We identified three novel and one previously described GJA1 mutation in two large ODDD families and two sporadic ODDD cases. [Copyright &y& Elsevier]

We review the different strategies currently used to try to identify susceptibility genes for idiopathic autism. Although identification of genes is usually straightforward in Mendelian disorders, it has proved to be much more difficult to establish in polygenic disorders like autism. Neither genome screens of affected siblings nor the large number of association studies using candidate genes have resulted in finding autism susceptibility genes. We focus on the alternative approach of 'positional cloning' through chromosomal aberrations in individuals with autism. In particular, balanced aberrations such as reciprocal translocations or inversions offer a unique opportunity, since only the genes in the breakpoint regions are candidate genes. This approach, in combination with others, is likely to produce results in the coming years. [ABSTRACT FROM AUTHOR]

Heterotaxia is an aetiologically heterogeneous condition caused by an abnormal left-right axis formation, resulting in reversed left-right polarity of one or more organ systems. In a patient with heterotaxia and a de novo reciprocal translocation t(6;18)(q21;q21), we found that the PA26 gene was disrupted by the 6q21 breakpoint. Northern blot analysis showed decreased expression of the PA26 gene in an Epstein-Barr virus-transformed cell line of this patient. During early embryogenesis of Xenopus, the orthologue of PA26, XPA26 is exclusively expressed in the notochord, a midline structure. This further supports a possible role of PA26 in human situs determination. Mutation analysis of human PA26 gene in 40 unrelated individuals with unexplained heterotaxia failed to identify mutations, indicating that PA26 mutations are not a frequent cause of heterotaxia in humans. Analysis of the PA26 gene structure resulted in the identification of a novel PA26-related gene family, which we have named the sestrin family, and which comprises three closely related genes in human and in mouse. [ABSTRACT FROM AUTHOR]

Segmental duplications or low-copy repeats (LCRs) on chromosome 22q11 have been implicated in several chromosomal rearrangements. The presence of AT-rich regions in these duplications may lead to the formation of hairpin structures, which facilitate chromosomal rearrangement. Here we report the involvement of such a low-copy repeat in a t(X;22) associated with a neural tube defect. Molecular analysis of the chromosomal breakpoints revealed that the chromosome 22 breakpoint maps in the palindromic non-AT-rich NF1 -like region of low-copy repeat B (LCR-B). No palindromic region was encountered near the breakpoint on chromosome X. Our findings confirm that there is no single mechanism leading to translocations with chromosome 22q11 involvement. Because LCR-B does not contain genes involved in neural tube development, we believe that the gene responsible for the observed phenotype is most likely localized on chromosome X. [ABSTRACT FROM AUTHOR]

Velo-cardio-facial syndrome (VCFS) is mostly associated with deletions of chromosome 22q11, and is thought to be characterized by an increased frequency of major psychiatric disorders. Sixteen patientsadults with VCFS and psychiatric symptoms were evaluated using a semi-structured investigation of history, symptoms, signs and behaviour. All available data were used in consensus meetings to obtain a classifiable diagnostic category. In contrast to other reports, no categorical diagnosis could be established. Instead, a quite specific psychological, behavioural and psychopathological constellation emerged that should most adequately be denominated as a VCFS-psychiatric syndrome. It is concluded that VCFS is associated with a specific psychopathological syndrome. [Copyright &y& Elsevier]

Describes a family with autosomal dominant isolated velopharyngeal incompetence, a velopgharyngeal disorder. Manifestations of the disease; Hypernasal speech of the patients; Role of soft palate in the velopharyngeal insufficiency.

Focuses on a study which investigated the genotype-phenotype mutations of tricho-rhino-phalangeal syndrome (TRPS) in patients with TRPS I and TRPS III. Description of TRPS sub-types; Evaluation on the degree of brachydactyly symptoms in patients with TRPS III; Spectrum of TRPS1 mutations.

Presents a letter to the editor on the causal role of the Aristaless-related homeobox gene in the origin of the encephalocele and endocrine defects in a patient.

Ring chromosome 7 is an unusual chromosome anomaly. Here we describe a patient with ring chromosome 7 and we show that both subtelomeres are still present. The diagnosis agrees with ‘ring syndrome’. This report helps to further delineate the clinical manifestations of ‘ring syndrome’ and to distinguish the phenotypic consequences of the presence of a ring chromosome 7 from the phenotypic consequences of terminal chromosome 7 submicroscopic deletions. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented about a case of left isomerism with fetal heart abnormalities.

An abstract of the conference paper "Rothmund-Thomson syndrome: Immuno-osseous challenges," by I. Meyts and colleagues is presented.

An abstract of the conference paper "Flow of patients with isolated congenital diaphragmatic hernia following referral to a fetal surgery unit" by E. Done and colleagues is presented.

Background: Disrupted sleep in children may lead to multiple behavioural problems that affect the individual and the family. The aim of this study was to compare sleep behaviour and sleep disorders in children with VCFS with those of their siblings and to determine the severity and pattern of the sleep problems. Method: Parents completed the Children’s Sleep Habits Questionnaire (CSHQ) (Owens et al., 2000) for 31 children with VCFS (mean age 10 years). This instrument has good psychometric properties and validity. It includes items relating to a number of key sleep domains grouped conceptually into eight subscales reflecting: (1) Bedtime Resistance; (2) Sleep Onset Delay; (3) Sleep Duration; (4) Sleep Anxiety; (5) Night Wakings; (6) Parasomnias; (7) Sleep Disordered Breathing; (8) Daytime Sleepiness. Total Sleep Disturbance Score includes all items of the eight subscales. Higher scores are indicative of more disturbed sleep. Results: The severity of sleep problems in the VCFS group was reported by parents as being significantly higher than in the sibling group (mean score 42.97 and 36.55, respectively; p < 0.001). Values for five of eight sleep subscales including bedtime resistance, sleep anxiety, night waking, parasomnias and daytime sleepiness were significantly (p < 0.001) higher in the VCFS group. Conclusion: Parents report that sleep problems are significantly more severe in children with VCFS compared to their siblings, and that the pattern appears diverse. Sleep problems in children with VCFS require further research and clinical attention. [ABSTRACT FROM AUTHOR]