Publications by authors named "Karin Weiss"

PDSS1 mutations hamper Coenzyme Q10 biosynthesis and cause a rare multisystem mitochondrial disease characterized by diverse clinical features and limited treatment options. To date, renal involvement has been reported in only one patient. We report a new female patient with compound heterozygous PDSS1 mutations and the clinical outcome following a trial of Coenzyme Q10 therapy.

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An increasing number of individuals with intellectual developmental disorder (IDD) and heterozygous variants in BCL11A are identified, yet our knowledge of manifestations and mutational spectrum is lacking. To address this, we performed detailed analysis of 42 individuals with BCL11A-related IDD (BCL11A-IDD, a.k.

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  • Rapid trio genome sequencing (rtGS) is being implemented in Israeli neonatal intensive care units (NICUs) to provide advanced care for critically ill newborns suspected of having genetic issues.
  • A study conducted from October 2021 to December 2022 involved 130 neonates, leading to a diagnostic rate of 50% for disease-causing genetic variants and 11% for variants of unknown significance (VUS).
  • Results showed a mean turnaround time for rapid reports of 7 days, with high engagement from medical staff regarding the clinical utility of the results (82% response rate to questionnaires).
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  • Arrhythmogenic cardiomyopathy (AC) is a serious inherited heart condition caused by the replacement of heart muscle cells (cardiomyocytes) with fibrous and fatty tissue, leading to dangerous heart rhythms and potential heart failure, with genetic variants in the DSG2 gene being linked to this disease.* -
  • A specific variant of DSG2, called Ser194Leu, was analyzed in a patient with AC, where advanced imaging techniques (electron microscopy) and tissue staining revealed structural abnormalities and reduced protein expression in heart cells.* -
  • The findings suggest that the Ser194Leu variant is a harmful mutation contributing to arrhythmogenic left ventricular cardiomyopathy, underlining the importance of accurate genetic variant classification for patient care.*
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Increasingly, next-generation sequencing (NGS) is becoming an invaluable tool in the diagnosis of unexplained acute neurological disorders, such as acute encephalopathy/encephalitis. Here, we describe a brief series of pediatric patients who presented at the pediatric intensive care unit with severe acute encephalopathy, initially suspected as infectious or inflammatory but subsequently diagnosed with a monogenic disorder. Rapid exome sequencing was performed during the initial hospitalization of three unrelated patients, and results were delivered within 7-21 days.

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  • This study focused on identifying genetic factors contributing to end-stage kidney disease (ESKD) in a minority group (Druze) in Israel, where existing data on genetic causes of chronic kidney disease are limited, particularly for minority populations.
  • Researchers conducted whole-exome sequencing on 94 Druze patients undergoing dialysis, discovering genetic etiologies in about 18% of participants, including a novel WDR19 variant and other known genes associated with kidney disease.
  • The findings highlight the importance of genetic testing in minority groups with high rates of chronic kidney disease, suggesting that certain genetic markers may go undiagnosed without comprehensive analysis, given that clinical diagnoses often did not match the final genetic results.
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Purpose: Exome sequencing (ES) is a powerful tool that facilitates the diagnosis of patients with rare Mendelian syndromes. In 2018 the Israeli Ministry of Health initiated a national pilot program that funds ES for outpatients with global developmental delay (GDD). Here, we describe the 3-year impact of this program on patient care in a single tertiary hospital.

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Background: SUMOylation involves the attachment of small ubiquitin-like modifier (SUMO) proteins to specific lysine residues on thousands of substrates with target-specific effects on protein function. Sentrin-specific proteases (SENPs) are proteins involved in the maturation and deconjugation of SUMO. Specifically, SENP7 is responsible for processing polySUMO chains on targeted substrates including the heterochromatin protein 1α (HP1α).

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Squamous cell carcinoma antigen recognized by T cells 3 (SART3) is an RNA-binding protein with numerous biological functions including recycling small nuclear RNAs to the spliceosome. Here, we identify recessive variants in SART3 in nine individuals presenting with intellectual disability, global developmental delay and a subset of brain anomalies, together with gonadal dysgenesis in 46,XY individuals. Knockdown of the Drosophila orthologue of SART3 reveals a conserved role in testicular and neuronal development.

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  • The blood-brain barrier (BBB) regulates the central nervous system and is linked to neurodevelopmental disorders (NDDs), especially in infants with intracerebral hemorrhage (ICH).
  • Researchers identified a rare disease trait in 13 individuals from 8 families due to a genetic variant in the ESAM gene, affecting endothelial cell function and leading to developmental issues.
  • The study highlights the connection between endothelial dysfunction and NDDs, suggesting the emergence of a new category of diseases called "tightjunctionopathies."
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  • * Researchers analyzed exome sequencing data from over 3,000 Israeli individuals to identify potentially pathogenic genetic variants across various ancestries, detecting variants not included in existing screening panels, particularly for Ashkenazi Jews and Muslim Arabs.
  • * The study emphasizes the importance of a community-driven approach in improving carrier screening by discovering previously overlooked variants and ensuring that screening panels are more inclusive and equitable for diverse populations.
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Background: Autosomal recessive conditions are common in consanguineous populations. Since consanguinity is common in the Israeli Arab population, we evaluated the rate of MUTYH polyposis (MAP) among polyposis patients in this population and studied Pathogenic Variants (PVs) spectrum.

Methods: We reviewed health records of all Arab and Druze polyposis patients referred for counseling during 2013-2020 who fulfilled the Israeli Genetic Society criteria for MUTYH/APC testing, in a tertiary center in Northern Israel and four additional gastro-genetic clinics in Israel.

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Purpose: KLHL20 is part of a CUL3-RING E3 ubiquitin ligase involved in protein ubiquitination. KLHL20 functions as the substrate adaptor that recognizes substrates and mediates the transfer of ubiquitin to the substrates. Although KLHL20 regulates neurite outgrowth and synaptic development in animal models, a role in human neurodevelopment has not yet been described.

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Biallelic pathogenic variants in SZT2 result in a neurodevelopmental disorder with shared features, including early-onset epilepsy, developmental delay, macrocephaly, and corpus callosum abnormalities. SZT2 is as a critical scaffolding protein in the amino acid sensing arm of the mTORC1 signalling pathway. Due to its large size (3432 amino acids), lack of crystal structure, and absence of functional domains, it is difficult to determine the pathogenicity of SZT2 missense and in-frame deletions, but these variants are increasingly detected and reported by clinical genetic testing in individuals with epilepsy.

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Background: Monogenic neurodegenerative diseases represent a heterogeneous group of disorders caused by mutations in genes involved in various cellular functions including autophagy, which mediates degradation of cytoplasmic contents by their transport into lysosomes. Abnormal autophagy is associated with hereditary ataxia and spastic paraplegia, amyotrophic lateral sclerosis and frontal dementia, characterised by intracellular accumulation of non-degraded proteins. We investigated the genetic basis of complex HSP in a consanguineous family of Arab-Muslim origin, consistent with autosomal recessive inheritance.

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Background And Objectives: Atypical hemolytic uremic syndrome (aHUS) is mostly attributed to dysregulation of the alternative complement pathway (ACP) secondary to disease-causing variants in complement components or regulatory proteins. Hereditary aHUS due to C3 disruption is rare, usually caused by heterozygous activating mutations in the gene, and transmitted as autosomal dominant traits. We studied the molecular basis of early-onset aHUS, associated with an unusual finding of a novel homozygous activating deletion in C3.

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Inherited liver diseases may present in infancy as cholestatic jaundice progressing to severe hepatic dysfunction. Congenital cytomegalovirus (cCMV) infection may initially involve the liver, yet in otherwise healthy hosts rarely leads to long-term hepatic disease. We report a series of three patients, diagnosed with hereditary liver diseases: progressive familial intrahepatic cholestasis (PFIC) type IV, alpha 1 anti-trypsin deficiency (A1ATD) and Alagille syndrome (ALGS), who were also diagnosed with cCMV infection.

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  • TCF7L2 is a gene that plays a crucial role in the Wnt signaling pathway and has been linked to conditions like intellectual disability and autism, though the details are still unclear.
  • This study examines 11 individuals with new mutations in TCF7L2, highlighting that these mutations can be either truncating or missense, with the latter mainly affecting a specific functional region of the protein.
  • Common traits among the affected individuals include childhood developmental delays, with most achieving normal intelligence later, along with potential eye problems, facial differences, orthopedic issues, and additional neuropsychiatric conditions like autism and ADHD.
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Germline pathogenic variants (PVs) in BRCA1/BRCA2 are well-established risk factors for breast cancer (BC) and/or ovarian cancer (OC). Founder PVs have been described in BRCA1/ BRCA2 in several genetic isolates. The Christian Arab population in the Middle East is a relatively isolated ethnic group, yet founder, or recurrent BRCA1/BRCA2 PVs have not been reported in this population.

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RBL2/p130, a member of the retinoblastoma family of proteins, is a key regulator of cell division and propagates irreversible senescence. RBL2/p130 is also involved in neuronal differentiation and survival, and eliminating Rbl2 in certain mouse strains leads to embryonic lethality accompanied by an abnormal central nervous system (CNS) phenotype. Conflicting reports exist regarding a role of RBL2/p130 in transcriptional regulation of DNA methyltransferases (DNMTs), as well as the control of telomere length.

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Deletion 1p36 (del1p36) syndrome is the most common human disorder resulting from a terminal autosomal deletion. This condition is molecularly and clinically heterogeneous. Deletions involving two non-overlapping regions, known as the distal (telomeric) and proximal (centromeric) critical regions, are sufficient to cause the majority of the recurrent clinical features, although with different facial features and dysmorphisms.

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