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Article
Open AccessVariant-specific pathophysiological mechanisms of AFF3 differently influence transcriptome profiles
We previously described the KINSSHIP syndrome, an autosomal dominant disorder associated with intellectual disability (ID), mesomelic dysplasia and horseshoe kidney, caused by de novo variants in the degron of...
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Article
Open AccessHeterozygous loss-of-function variants in DOCK4 cause neurodevelopmental delay and microcephaly
Neurons form the basic anatomical and functional structure of the nervous system, and defects in neuronal differentiation or formation of neurites are associated with various psychiatric and neurodevelopmental...
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Article
Open AccessEvaluating the association of biallelic OGDHL variants with significant phenotypic heterogeneity
Biallelic variants in OGDHL, encoding part of the α-ketoglutarate dehydrogenase complex, have been associated with highly heterogeneous neurological and neurodevelopmental disorders. However, the validity of this...
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Article
Open AccessAberrant expression of agouti signaling protein (ASIP) as a cause of monogenic severe childhood obesity
Here we report a heterozygous tandem duplication at the ASIP (agouti signaling protein) gene locus causing ubiquitous, ectopic ASIP expression in a female patient with extreme childhood obesity. The mutation plac...
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Article
Open AccessAltered gene expression profiles impair the nervous system development in individuals with 15q13.3 microdeletion
The 15q13.3 microdeletion has pleiotropic effects ranging from apparently healthy to severely affected individuals. The underlying basis of the variable phenotype remains elusive. We analyzed gene expression u...
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Article
Open AccessPhenotype-tissue expression and exploration (PTEE) resource facilitates the choice of tissue for RNA-seq-based clinical genetics studies
RNA-seq emerges as a valuable method for clinical genetics. The transcriptome is “dynamic” and tissue-specific, but typically the probed tissues to analyze (TA) are different from the tissue of interest (TI) b...
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Article
Open AccessEIF3F-related neurodevelopmental disorder: refining the phenotypic and expanding the molecular spectrum
An identical homozygous missense variant in EIF3F, identified through a large-scale genome-wide sequencing approach, was reported as causative in nine individuals with a neurodevelopmental disorder, characterized...
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Article
Open AccessGermline AGO2 mutations impair RNA interference and human neurological development
ARGONAUTE-2 and associated miRNAs form the RNA-induced silencing complex (RISC), which targets mRNAs for translational silencing and degradation as part of the RNA interference pathway. Despite the essential n...
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Article
Open AccessDisruptive mutations in TANC2 define a neurodevelopmental syndrome associated with psychiatric disorders
Postsynaptic density (PSD) proteins have been implicated in the pathophysiology of neurodevelopmental and psychiatric disorders. Here, we present detailed clinical and genetic data for 20 patients with likely ...
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Article
Biallelic loss of human CTNNA2, encoding αN-catenin, leads to ARP2/3 complex overactivity and disordered cortical neuronal migration
Neuronal migration defects, including pachygyria, are among the most severe developmental brain defects in humans. Here, we identify biallelic truncating mutations in CTNNA2, encoding αN-catenin, in patients with...
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Article
De novo variants in neurodevelopmental disorders with epilepsy
Epilepsy is a frequent feature of neurodevelopmental disorders (NDDs), but little is known about genetic differences between NDDs with and without epilepsy. We analyzed de novo variants (DNVs) in 6,753 parent–...
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Article
Open AccessGenetic screening confirms heterozygous mutations in ACAN as a major cause of idiopathic short stature
Short stature is a common pediatric disorder affecting 3% of the population. However, the clinical variability and genetic heterogeneity prevents the identification of the underlying cause in about 80% of the ...
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Article
Open AccessAMPA-receptor specific biogenesis complexes control synaptic transmission and intellectual ability
AMPA-type glutamate receptors (AMPARs), key elements in excitatory neurotransmission in the brain, are macromolecular complexes whose properties and cellular functions are determined by the co-assembled consti...
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Article
Open AccessSPATA5 mutations cause a distinct autosomal recessive phenotype of intellectual disability, hypotonia and hearing loss
We examined an extended, consanguineous family with seven individuals with severe intellectual disability and microcephaly. Further symptoms were hearing loss, vision impairment, gastrointestinal disturbances,...
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Article
The Role of Periodontal Ligament Cells in Delayed Tooth Eruption in Patients with Cleidocranial Dysostosis*
The clinical appearance of patients with cleidocranial dysplasia (CCD), which is caused by mutations in the RUNX2 gene, is characterized by anomalies of the clavicles, thorax, spine, pelvis and extremities and...
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Article
Brief Report: No Association Between Premorbid Adjustment in Adult-Onset Schizophrenia and Genetic Variation in Dysbindin
Whereas Dysbindin is considered a schizophrenia vulnerability gene, there is no consistency of findings. Phenotype refinement approaches may help to increase the genetic homogeneity and thus reconcile conflicting...
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Article
Open AccessMonoamine related functional gene variants and relationships to monoamine metabolite concentrations in CSF of healthy volunteers
Concentrations of monoamine metabolites in human cerebrospinal fluid (CSF) have been used extensively as indirect estimates of monoamine turnover in the brain. CSF monoamine metabolite concentrations are partl...
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Article
No evidence for DUP25 in patients with panic disorder using a quantitative real-time PCR approach
A duplication of chromosome 15q24-q26 (DUP25) has been reported to be associated with anxiety disorders. We tested for the presence of DUP25 in a sample of 50 patients with panic disorder and 50 controls using...
