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The in-depth characterization of patients with common variable immunodeficiency (CVID) is a recent advancement, revealing a complex genetic landscape.
Ciliopathies are a group of neurodevelopmental disorders characterized by the dysfunction of the primary cilium.
While mostly de novo truncating variants in SCAF4 were recently identified in 18 individuals with variable neurodevelopmental phenotypes, knowledge on the molecular and clinical spectrum is still limited.
Das Institut für Medizinische Genetik der Universität Zürich hat während der Festtage an bestimmten Tagen und zu bestimmten Uhrzeiten geöffnet. Hier finden Sie alle Informationen dazu.
This study details a novel syndromic form of autosomal recessive intellectual disability resulting from recessive variants in GTF3C3, encoding a key component of the DNA-binding transcription factor IIIC, which has a conserved role in RNA polymerase III-mediated transcription.
Children represent a large and vulnerable patient group. However, the evidence base for most paediatric diagnostic and therapeutic procedures remains limited or is often inferred from adults.
geboren in Hamburg am 15.08.1935, verstorben 31. Oktober 2023 in Salt Lake City, Utah, U.S.A
Pediatric Acute B-Lymphoblastic Leukemia Presenting as Hypereosinophilia With Lung Involvement and Elevated Immunoglobulin E Levels.
Hydrocephalus and Dandy-Walker malformation are among the most common congenital brain anomalies.
Ab 2. November finden Sie das Kinderspital Zürich an neuer Adresse.
Künftig wird die hochstehende medizinische und pflegerische Betreuung Ihres Kindes in einem modernen Neubau sicher gestellt.
Joubert Syndrome gene dysfunction in zebrafish leads to abnormal brain cilia, altered transcription of neuron-associated genes and abnormal swimming behaviour despite normal brain morphology.
De novo variants in cullin-3 ubiquitin ligase (CUL3) have been strongly associated with neurodevelopmental disorders (NDDs), but no large case series have been reported so far. Here, we aimed to collect sporadic cases carrying rare variants in CUL3, describe the genotype–phenotype correlation, and investigate the underlying pathogenic mechanism.
The contribution of splicing variants to molecular diagnostics of inherited diseases is reported to be less than 10%.
Ein Gen namens ZNRF3, das bei Krebs eine Rolle spielt, bringt auch das Gehirn durcheinander. Ist eine der beiden Gen-Kopien defekt, wird das Gehirn entweder zu gross oder zu klein, was diverse Krankheitssymptome zur Folge hat.
Background
Agammaglobulinemia due to variants in IGLL1 has traditionally been considered an exceedingly rare form of severe B-cell deficiency, with only eight documented cases in the literature. Surprisingly, the first agammaglobulinemic patient identified by newborn screening (NBS) through quantification of kappa-deleting recombination excision circles harbored variants in IGLL1.
Zinc and RING finger 3 (ZNRF3) is a negative-feedback regulator of Wnt/β-catenin signaling, which plays an important role in human brain development.
Alterations in the X-linked recessive DMD gene cause dystrophinopathies with a broad clinical spectrum most commonly ranging from Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy (BMD) to cardiomyopathy or intellectual disability.
While it is widely thought that de novo mutations (DNMs) occur randomly, we previously showed that some DNMs are enriched because they are positively selected in the testes of aging men. These “selfish” mutations cause disorders with a shared presentation of features, including exclusive paternal origin, significant increase of the father’s age, and high apparent germline mutation rate.
To present a case series of novel CHD2 variants in patients presenting with genetic epileptic and developmental encephalopathy.
To support clinical decision making, all five Swiss academic institutions for Medical Genetics joined forces with the Swiss Institute of Bioinformatics (SIB) to create SwissGenVar as a user-friendly nationwide repository and sharing platform for genetic variant data .
The purpose of this study was to assess the added diagnostic value of whole genome sequencing (WGS) for patients with inherited retinal diseases (IRDs) who remained undiagnosed after whole exome sequencing (WES).
Ruxandra Bachmann-Gagescu wurde Oktober 2023 als ausserordentliche Doppel-Professorin für Entwicklungsgenetik am Institut für Molekularbiologie der Mathematisch- Naturwissenschaftlichen Fakultät und am Institut für Medizinische Genetik der Medizinischen Fakultät der Universität Zürich ernannt.
Background
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 AFF3. Mouse knock-ins and overexpression in zebrafish provided evidence for a dominant-negative mode of action, wherein an increased level of AFF3 resulted in pathological effects.
Deubiquitination is critical for the proper functioning of numerous biological pathways such as DNA repair, cell cycle progression, transcription, signal transduction, and autophagy. Accordingly, pathogenic variants in deubiquitinating enzymes (DUBs) have been implicated in neurodevelopmental disorders (ND) and congenital abnormalities. ATXN7L3 is a component of the DUB module of the SAGA complex, and two other related DUB modules, and serves as an obligate adaptor protein of 3 ubiquitin-specific proteases (USP22, USP27X or USP51).
Cilia defects lead to scoliosis in zebrafish, but the underlying pathogenic mechanisms are poorly understood and may diverge depending on the mutated gene.
Anoctamins are a family of Ca2+-activated proteins that may act as ion channels and/or phospholipid scramblases with limited understanding of function and disease association. Here, we identified five de novo and two inherited missense variants in ANO4 (alias TMEM16D) as a cause of fever-sensitive developmental and epileptic or epileptic encephalopathy (DEE/EE) and generalized epilepsy with febrile seizures plus (GEFS+) or temporal lobe epilepsy.
To date 11 patients with Coffin-Siris syndrome type 7 (OMIM 618027) have been described since the first literature report. All reported patients carried de novo variants with presumed dominant negative effect, which localized in the PHD1/PHD2 domains of DPF2.
Read the full article here.
The physical interactome of a protein can be altered upon perturbation, modulating cell physiology and contributing to disease. Identifying interactome differences of normal and disease states of proteins could help understand disease mechanisms, but current methods do not pinpoint structure-specific PPIs and interaction interfaces proteome-wide.
Wir möchten Sie darüber informieren, dass das Institut am 1. Mai und bis 12 Uhr am 2. Mai eine Umstellung des in- und externen Netzwerks durchführt.
Epithelial cells comprising the choroid plexus (CP) form a crucial barrier between the blood
and the cerebrospinal fluid, thereby assuming a central position in brain homeostasis and signaling.
Mounting evidence suggests that the impairment of CP function may be a significant contributor to
Alzheimer’s disease (AD) pathogenesis.
Read the full article here.
Das Institut ist ab Gründonnerstag, 16.00 Uhr, bis und mit Ostermontag, 1. April, geschlossen.
Bitte beachten sie das wir noch bis 17:00 Uhr Proben annehmen. Am Dienstag den 2. April sind wir wieder wie gewohnt für Sie da!
Das Institut für Medizinische Genetik hatte einen E-Mail-Störung. Dies ist nun behoben. Weitere Informationen finden Sie in diesem Artikel.
SNURPORTIN-1, encoded by SNUPN, plays a central role in the nuclear import of spliceosomal small nuclear ribonucleoproteins. However, its physiological function remains unexplored. In this study, we investigate 18 children from 15 unrelated families who present with atypical muscular dystrophy and neurological defects.
Read the full article here.
Cilia defects lead to scoliosis in zebrafish, but the underlying pathogenic mechanisms are poorly understood and may diverge depending on the mutated gene. We dissected the mechanisms of scoliosis onset in a zebrafish mutant for the rpgrip1l gene encoding a ciliary transition zone protein. rpgrip1l mutant fish developed scoliosis with near-total penetrance but asynchronous onset in juveniles.
Read the full article here.
Joubert Syndrome (JBTS) is a neurodevelopmental ciliopathy defined by a highly specific midbrain-hindbrain malformation, variably associated with additional neurological features. JBTS displays prominent genetic heterogeneity with >40 causative genes that encode proteins localising to the primary cilium, a sensory organelle that is essential for transduction of signalling pathways during neurodevelopment, among other vital functions.
Read this preprint in full in our Preprint section.
This thesis aims to use bioinformatic approaches to elucidate the underlying genetic causes of three different diseases.
Systemic amyloidoses are rare protein-folding diseases with heterogeneous, often nonspecific clinical presentations. To better understand systemic amyloidoses and to apply state-of-the-art diagnostic pathways and treatment, the interdisciplinary Amyloidosis Network was founded in 2013 at University Hospital Zurich. In this respect, a registry was implemented to study the characteristics and life expectancy of patients with amyloidosis within the area covered by the network. Patient data were collected retrospectively for the period 2005–2014 and prospectively from 2015 onwards.
Mowat-Wilson syndrome (MOWS) is a rare congenital disease caused by haploinsufficiency of ZEB2, encoding a transcription factor required for neurodevelopment.
Read this article in full at the European Journal of Human Genetics.
Heterozygous variants in RAR-related orphan receptor B (RORB) have recently been associated with susceptibility to idiopathic generalized epilepsy. Read this article in full at Neurology
(Artikel auf Englisch)
Neurodevelopmental proteasomopathies represent a distinctive category of neurodevelopmental disorders (NDD) characterized by genetic variations within the 26S proteasome, a protein complex governing eukaryotic cellular protein homeostasis. Read the full pre-print article online at medRxiv
(Artikel auf Englisch)
The intricacies of Alzheimer’s disease pathogenesis are being increasingly illuminated by the exploration of epigenetic mechanisms, particularly DNA methylation. This review comprehensively surveys recent human-centered studies that investigate whole genome DNA methylation in Alzheimer’s disease neuropathology.
(Artikel auf Englisch)
Somatic variants in the NOTCH pathway regulator FBXW7 are frequently seen in a variety of malignancies. Read this publication online in the American Journal of Medical Genetics
(Artikel auf Englisch)
