Publications by authors named "Iascone M"

Background: the protein phosphatase 3 catalytic subunit alpha (PPP3CA) gene encodes for the alpha isoform of the calcineurin catalytic subunit, which controls the phosphorylation status of many targets. Currently, 23 pathogenic variants of PPP3CA are known, with clinical manifestations varying by mutation type and domain.

Results: through whole exome sequencing, we found two de novo variants in PPP3CA: a frameshift variant predicted leading to a truncated protein in Pt.

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Spontaneous coronary artery dissection (SCAD) is a relevant non-atherosclerotic cause of acute coronary syndrome with a complex genetic architecture. Recent discoveries have highlighted the potential role of miRNAs and protein-coding genes involved in the processing of small RNAs in the pathogenesis of SCAD. Furthermore, there may be a connection between SCAD and the increased cardiovascular risk observed in fragile X premutation carriers as well as a correlation with pathogenetic variants in genes encoding for collagen and extracellular matrix, which are related to connective tissue disorders (CTDs).

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: The pathogenetic role of 15q11.2 Copy Number Variations (CNVs) remains contentious in the scientific community, as microdeletions and microduplications in this region are linked to neurodevelopmental disorders with variable expressivity. This study aims to explore the diagnostic utility of Exome Sequencing (ES) in a cohort of pediatric patients with 15q11.

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CTNND1 is a gene located in 11q12.1, encoding for p120 catenin, a protein involved in maintaining adherent junctions, regulating the epithelial-mesenchymal transition, and transcriptional signaling of different cellular pathways. Pathogenic variants in CTNND1 are classically associated with isolated cleft palate and Blefaro-cheilo-dontic syndrome, an autosomal dominant condition characterized by abnormalities of the eyelid.

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DDX17 is an RNA helicase shown to be involved in critical processes during the early phases of neuronal differentiation. Globally, we compiled a case-series of 11 patients with neurodevelopmental phenotypes harbouring de novo monoallelic variants in DDX17. All 11 patients in our case series had a neurodevelopmental phenotype, whereby intellectual disability, delayed speech and language, and motor delay predominated.

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Background/objectives: Identifying novel variants in very rare disease genes can be challenging when patients exhibit a complex phenotype that expands the one described, and we provide such an example here. A few terminal truncating variants in cause spastic paraplegia (SP), intellectual disability (ID), nystagmus, and obesity (SINO, MIM #617296). Prompted by the result of next-generation sequencing on a patient referred for SP associated with complex brain dysmorphisms, we reviewed the phenotype of SINO patients focusing on their brain malformations, mainly described in prenatal age and first years of life, and tried to understand if the predicted effect of the mutant kidins220 may have caused them.

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Objective: Biallelic titin truncating variants (TTNtv) have been associated with a wide phenotypic spectrum, ranging from complex prenatal muscle diseases with dysmorphic features to adult-onset limb-girdle muscular dystrophy, with or without cardiac involvement. Given the size and complexity of TTN, reaching an unequivocal molecular diagnosis and precise disease prognosis remains challenging.

Methods: In this case series, 12 unpublished cases and one already published case with biallelic TTNtv were collected from multiple international medical centers between November 2022 and September 2023.

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Background: Dilated cardiomyopathy (DCM) is an etiologically heterogeneous group of diseases of the myocardium. With the rapid evolution in laboratory investigations, genetic background is increasingly determined including many genes with variable penetrance and expressivity. Biallelic NEXN variants are rare in humans and associated with poor prognosis: fetal and perinatal death or severe DCMs in infants.

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Objectives: To provide a comprehensive description of neuroradiologic findings in a patient with a probable pathogenic variant of , particularly in relation to pontine and cerebellar hypoplasia.

Methods: We first report prenatal and postnatal neuroradiologic phenotype of a female patient carrying a likely pathogenic variant and discuss its function.

Results: An ultrasound shows borderline ventriculomegaly, rotated cerebellar vermis, and dysgenetic corpus callosum.

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Purpose: Epigenetic dysregulation has been associated with many inherited disorders. RBBP5 (HGNC:9888) encodes a core member of the protein complex that methylates histone 3 lysine-4 and has not been implicated in human disease.

Methods: We identify 5 unrelated individuals with de novo heterozygous variants in RBBP5.

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Article Synopsis
  • AJAP1 is a protein linked to brain diseases and is found in neurons, specifically in dendrites, where it plays a role in recruiting GABA type B receptors (GBRs) to presynaptic sites.
  • Several genetic variants of AJAP1, including the p.(W183C), have been associated with epilepsy and neurodevelopmental disorders, particularly affecting its ability to bind GBRs.
  • Mice lacking functional AJAP1 showed decreased levels of presynaptic GBRs, leading to impaired synaptic inhibition and plasticity, highlighting the importance of AJAP1 in regulating neurotransmitter release.
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  • - Rubinstein-Taybi syndrome (RTS) is a rare genetic disorder that involves intellectual disabilities, unique facial features, and unusually large thumbs and toes, with most cases linked to specific genetic variants.
  • - The syndrome is considered a chromatinopathy due to the mutations affecting genes involved in epigenomic regulation, making it difficult to diagnose based solely on phenotype due to its varied presentation.
  • - A case study of a patient with a rare form of RTS highlights the issue of potential underdiagnosis for milder cases, suggesting that combining phenotype-based diagnostics with advanced genetic sequencing techniques may improve detection rates.
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  • * A study identified 25 individuals with new variations in the MSL2 gene, who exhibited NDD symptoms such as developmental delays, coordination problems, and autism spectrum disorder, along with other health concerns.
  • * iPSCs from affected individuals showed reduced MSL2 levels and changes in gene expression, leading to the characterization of a new MSL2-related disorder with unique clinical markers and a specific DNA episignature for diagnosis.
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  • Congenital diaphragmatic hernia (CDH) is a birth defect with different types, including Bochdalek and Morgagni hernias, and can occur in conditions like Marfan syndrome (MFS), which affects connective tissue.
  • A child with recurrent respiratory infections was found to have a Morgagni hernia via chest X-ray, leading to ongoing medical evaluations that confirmed a diagnosis of MFS with a mutation in the FBN1 gene.
  • The case emphasizes the need for continuous multidisciplinary monitoring for children diagnosed with CDH to identify and manage potential complications, such as cardiovascular issues related to MFS.
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  • The study utilized long-read sequencing (LRS) to analyze a patient diagnosed with Cornelia de Lange syndrome (CDLS), a genetic disorder related to defects in cohesin complex genes, particularly those located at 5p13.2.
  • Initial tests showed an abnormal chromosome structure (46,XY,t(5;15)(p13;q25)dn) but did not identify significant copy number variations or pathogenic alterations through standard methods like a-CGH and FISH.
  • LRS uncovered a chromothripsis event at 5p13.2, involving multiple chromosome breaks and rearrangements, which clarified the molecular cause of CDLS that traditional diagnostic techniques had missed, emphasizing LRS's value in clinical genetics.
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  • The article DOI: 10.3389/fneur.2022.1072256 has been corrected to address inaccuracies.
  • This correction aims to improve the reliability and accuracy of the information presented in the original study.
  • Readers are encouraged to refer to the updated version for the most accurate findings and interpretations.
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Mannosyl-oligosaccharide glucosidase - congenital disorder of glycosylation (MOGS-CDG) is determined by biallelic mutations in the mannosyl-oligosaccharide glucosidase (glucosidase I) gene. MOGS-CDG is a rare disorder affecting the processing of N-Glycans (CDG type II) and is characterized by prominent neurological involvement including hypotonia, developmental delay, seizures and movement disorders. To the best of our knowledge, 30 patients with MOGS-CDG have been published so far.

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Article Synopsis
  • The translation elongation factor eEF1A2 is crucial for binding aminoacyl-tRNA to the ribosome, and since 2012, 21 harmful variants have been linked to severe neurodevelopmental disorders, including epilepsy and intellectual disabilities.
  • A recent study gathered 26 patients with EEF1A2 variants, revealing a milder clinical profile than previously reported, with higher walking and language skills and lower rates of intellectual disability and epilepsy.
  • The research identified 8 new EEF1A2 variants and suggests that severe and moderate phenotypes are linked to specific protein regions affecting GTP exchange, while milder variants may affect secondary functions, contributing to a broader understanding
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Post-zygotic mosaicism is a well-known biological phenomenon characterized by the presence of genetically distinct lineages of cells in the same individual due to post-zygotic de novo mutational events. It has been identified in about 13% of Cornelia de Lange (CdLS) syndrome patients with a molecular diagnosis, an unusual high frequency. Here, we report the case of a patient affected by classic CdLS harboring post-zygotic mosaicism for two different likely pathogenic variants at the same nucleotide position in NIPBL.

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