Publications by authors named "Paria N Torbati"
Developmental and epileptic encephalopathies (DEEs) feature altered brain development, developmental delay and seizures, with seizures exacerbating developmental delay. Here we identify a cohort with biallelic variants in DENND5A, encoding a membrane trafficking protein, and develop animal models with phenotypes like the human syndrome. We demonstrate that DENND5A interacts with Pals1/MUPP1, components of the Crumbs apical polarity complex required for symmetrical division of neural progenitor cells.
View Article and Find Full Text PDFBackground: Plectinopathy-associated disorders are caused by mutations in the gene encoding Plectin protein. mutations cause a spectrum of diseases defined by varying degrees of signs, mostly with epidermolysis bullosa simplex with muscular dystrophy (EBS-MD) and plectinopathy-related disorder is limb-girdle muscular dystrophy type 2Q (LGMD2Q). Here we report three cases with EBS-MD and LGMD2Q disorders analyzed by exome sequencing followed by mutation confirmation.
View Article and Find Full Text PDFDevelopmental and epileptic encephalopathies (DEEs) are a heterogenous group of epilepsies in which altered brain development leads to developmental delay and seizures, with the epileptic activity further negatively impacting neurodevelopment. Identifying the underlying cause of DEEs is essential for progress toward precision therapies. Here we describe a group of individuals with biallelic variants in and determine that variant type is correlated with disease severity.
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- ECEL1 is linked to an autosomal recessive form of distal arthrogryposis, and the study examined a novel mutation (c.535A>G) identified in a family with affected boys and fetus through prenatal testing.
- Researchers conducted whole-exome sequencing and molecular dynamic simulations to analyze the differences between the normal and mutated ECEL1 proteins, validating the mutation presence in the affected family members.
- The study found significant structural differences in the ECEL1 protein due to the mutation, particularly its inability to bind zinc ions, which contributes to the neurodegenerative disorder, suggesting the findings could enhance our understanding of the mutation's effects on the protein.
Article Synopsis
- Advances in molecular diagnostics have shown that certain genetic variants linked to neurodegenerative diseases can also cause severe neurodevelopmental disorders when inherited in a biallelic manner.* -
- The study focuses on TOR1A-associated arthrogryposis multiplex congenita 5 (AMC5), revealing a range of clinical symptoms across a cohort of 57 individuals, including severe flexion contractures, developmental delays, and various motor issues.* -
- The research identified a phenotypic spectrum from mild symptoms to severe disabilities, with a notable survival rate of 71% and a median mortality age of 1.2 months, mainly due to complications like respiratory failure.*
Biallelic variants in OGDH encoding oxoglutarate dehydrogenase lead to a neurodevelopmental disorder characterized by global developmental delay, movement disorder, and metabolic abnormalities.
Genet Med
February 2023
Article Synopsis
- * Researchers used advanced techniques like exome sequencing and functional analysis to identify three novel homozygous variants in the OGDH gene, which is crucial for energy metabolism.
- * The findings suggest that these variants disrupt the normal function of the OGDH protein, leading to the observed neurodevelopmental disorder characterized by metabolic and movement abnormalities.
Background: Steroid resistant nephrotic syndrome (SRNS) represents a significant renal disease burden in childhood and adolescence. In contrast to steroid sensitive nephrotic syndrome (SSNS), renal outcomes are significantly poorer in SRNS. Over the past decade, extensive genetic heterogeneity has become evident while disease-causing variants are still only identified in 30% of cases in previously reported studies with proportion and type of variants identified differing depending on the age of onset and ethnical background of probands.
View Article and Find Full Text PDFImportin 8, encoded by IPO8, is a ubiquitously expressed member of the importin-β protein family that translocates cargo molecules such as proteins, RNAs, and ribonucleoprotein complexes into the nucleus in a RanGTP-dependent manner. Current knowledge of the cargoes of importin 8 is limited, but TGF-β signaling components such as SMAD1-4 have been suggested to be among them. Here, we report that bi-allelic loss-of-function variants in IPO8 cause a syndromic form of thoracic aortic aneurysm (TAA) with clinical overlap with Loeys-Dietz and Shprintzen-Goldberg syndromes.
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- PDXK is a gene responsible for producing a kinase that activates vitamin B6, crucial for various bodily functions, and mutations in this gene can lead to a specific type of nerve disease.
- Researchers identified a new harmful variant in the PDXK gene in two siblings, which resulted in an early-onset form of this nerve disease that responds to vitamin B6 treatment.
- Through advanced analysis techniques, the study found that this variant severely impaired the enzyme's function, leading to low vitamin levels, and emphasizes the importance of genetic screening for similar cases to enable effective treatment.
Cardiovascular diseases (CVDs) are one of the leading causes of morbidity and mortality. Standard therapies have failed to significantly increase patients' survival. Moreover, the majority of conventional screening procedures are ineffective for the diagnosis of CVDs at early stages.
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