Publications by authors named "Juan Pie"

Article Synopsis
  • - Cornelia de Lange syndrome (CdLS) is a rare genetic disorder that impacts physical development and cognitive abilities, primarily caused by mutations in genes linked to the cohesin complex, though many cases remain undiagnosed.
  • - The study presents a family case where multiple members have an intragenic duplication in the AFF2 gene, identified using advanced genomic technologies like high-resolution array Comparative Genomic Hybridization and next-generation sequencing.
  • - The research shows a clear correlation between the AFF2 gene mutation and the CdLS phenotype, with the affected individuals displaying significant changes in gene expression and X-inactivation patterns compared to an unaffected relative, suggesting that AFF2 should be included in molecular diagnosis for CdLS.
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Article Synopsis
  • Cornelia de Lange syndrome (CdLS) is a rare congenital disorder with diverse symptoms, including unique facial features, growth issues, limb reductions, and intellectual disability, with a classic and milder nonclassic phenotype.
  • Diagnosis can be challenging due to symptom overlap with other disorders, so consensus criteria and AI tools may assist in confirming cases.
  • Genetic causes primarily involve mutations in the NIPBL gene and others related to the cohesin complex, while about 15% of cases remain undiagnosed, indicating potential undiscovered genetic factors; treatment focuses on managing symptoms like gastro-esophageal reflux.
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Article Synopsis
  • Cornelia de Lange syndrome (CdLS) is a rare genetic disorder affecting various body systems, and this study focused on assessing the quality of life (QoL) of 33 individuals with CdLS, aged 4 to 21 years, using the Kidslife questionnaire.
  • The findings showed that participants had a below-median QoL, particularly in physical well-being, personal development, and self-determination, with key risk factors identified as variants in the NIPBL gene and significant behavioral and communication challenges.
  • The study calls for a holistic approach to CdLS that includes clinical, molecular, and psychosocial support, and emphasizes the importance of targeted interventions to improve QoL
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Article Synopsis
  • Cornelia de Lange Syndrome (CdLS) is a rare genetic disorder marked by a variety of symptoms including growth delays, upper limb issues, and other systemic problems, primarily caused by mutations in specific genes associated with the cohesin complex.
  • The majority of CdLS cases (over 60%) are linked to mutations in the NIPBL gene, which leads to the most severe form of the syndrome; other cohesin gene mutations typically result in milder symptoms.
  • The study analyzed the genetic factors in 716 individuals with CdLS to better understand the contributions of cohesin complex genes and identify potential new candidate genes, improving knowledge of genetic variations and their effects on CdLS manifestations.
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Article Synopsis
  • Neurodevelopmental disorder (-NDD) is a rare genetic condition known for causing developmental delays, distinct facial features, and birth defects, with heart disease (HD) commonly observed but under-researched.
  • In a study of 11 -NDD patients, 7 were found to have heart disease, including cases of ascending aortic dilatation and mitral valve prolapse, but overall cardiac function appeared normal compared to healthy controls.
  • The findings underscore the necessity of cardiac evaluations for all individuals with -NDD, noting a significant prevalence of heart abnormalities in this patient group, alongside new insights into specific heart issues previously undocumented in the syndrome.
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This study assesses a possible cardiac dysfunction in individuals with Cornelia de Lange syndrome (CdLS) without diagnosed congenital heart disease (CHD) and its association with other factors. Twenty patients and 20 controls were included in the study divided into three age-dependent groups (A: < 10 yrs, B: 10-20 yrs, C: > 20 yrs), and were evaluated using conventional echocardiography, tissue doppler imaging (TDI), two-dimensional speckle tracking and genetic and biochemical analyses. The left ventricular global longitudinal strain (GLS) was altered (< 15.

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Ultimate advances in genetic technologies have permitted the detection of transmitted cases of congenital diseases due to parental gonadosomatic mosaicism. Regarding Cornelia de Lange syndrome (CdLS), up to date, only a few cases are known to follow this inheritance pattern. However, the high prevalence of somatic mosaicism recently reported in this syndrome (∼13%), together with the disparity observed in tissue distribution of the causal variant, suggests that its prevalence in this disorder could be underestimated.

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Article Synopsis
  • * Key symptoms include neurodevelopmental delays, seizures, and a specific facial appearance, which can sometimes overlap with other syndromes like PACS2 and Wdr37.
  • * Research indicates that the mutated PACS1 protein may have harmful effects, inspiring potential treatments such as antisense oligonucleotides or targeting associated proteins to mitigate these effects.
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Cornelia de Lange syndrome (CdLS) is a multisystemic genetic disorder characterized by distinctive facial features, growth retardation, and intellectual disability, as well as various systemic conditions. It is caused by genetic variants in genes related to the cohesin complex. Single-nucleotide variations are the best-known genetic cause of CdLS; however, copy number variants (CNVs) clearly underlie a substantial proportion of cases of the syndrome.

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Article Synopsis
  • * The research reveals that somatic damaging NIPBL variants are often negatively selected in blood, and indicates a notable 13.1% prevalence of mosaicism among patients with a confirmed molecular diagnosis of CdLS.
  • * Most patients with mosaicism exhibit severe symptoms similar to those with stable (constitutive) pathogenic variants, but the types of genetic mutations remain consistent across both types, emphasizing the need for improved clinical management and genetic counseling for affected families.
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Schuurs-Hoeijmakers syndrome (SHMS) or Neurodevelopmental disorder is a rare disorder characterized by intellectual disability, abnormal craniofacial features and congenital malformations. SHMS is an autosomal dominant hereditary disease caused by pathogenic variants in the gene. PACS1 is a trans-Golgi-membrane traffic regulator that directs protein cargo and several viral envelope proteins.

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The gamma-1 isoform of casein kinase 1, the protein encoded by CSNK1G1, is involved in the growth and morphogenesis of cells. This protein is expressed ubiquitously among many tissue types, including the brain, where it regulates the phosphorylation of N-methyl-D-aspartate receptors and plays a role in synaptic transmission. One prior individual with a de novo variant in CSNK1G presenting with severe developmental delay and early-onset epilepsy has been reported.

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Cornelia de Lange syndrome (CdLS), Rubinstein-Taybi syndrome (RSTS), and KBG syndrome are three distinct developmental human disorders. Variants in seven genes belonging to the cohesin pathway, NIPBL, SMC1A, SMC3, HDAC8, RAD21, ANKRD11, and BRD4, were identified in about 80% of patients with CdLS, suggesting that additional causative genes remain to be discovered. Two genes, CREBBP and EP300, have been associated with RSTS, whereas KBG results from variants in ANKRD11.

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Article Synopsis
  • - The study focuses on the NIPBL/MAU2 complex, which is crucial for loading cohesin onto chromatin, and how mutations in NIPBL are linked to Cornelia de Lange syndrome (CdLS).
  • - A specific MAU2 variant causing CdLS was identified, which disrupts its interaction with NIPBL, yet other findings showed that cell lines can function normally despite having this mutation.
  • - The research indicates that cohesin loading can occur without the typical NIPBL/MAU2 interaction, suggesting an alternative mechanism that may help protect against serious genetic mutations and could inform understanding of various genetic disorders.
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RAD21 encodes a key component of the cohesin complex, and variants in RAD21 have been associated with Cornelia de Lange Syndrome (CdLS). Limited information on phenotypes attributable to RAD21 variants and genotype-phenotype relationships is currently published. We gathered a series of 49 individuals from 33 families with RAD21 alterations [24 different intragenic sequence variants (2 recurrent), 7 unique microdeletions], including 24 hitherto unpublished cases.

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Article Synopsis
  • Cornelia de Lange syndrome (CdLS) is challenging to diagnose due to its recognizable facial features and genetic diversity among affected individuals.
  • A study involving 49 patients with CdLS identified that the DeepGestalt technology and Face2Gene app effectively predicted CdLS as the top syndrome in 97.9% of cases.
  • The research suggests that using deep learning for image analysis can enhance diagnostic accuracy and potentially help differentiate between genetic subtypes of CdLS.
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Disorders/differences of sex development (DSD) cause profound psychological and reproductive consequences for the affected individuals, however, most are still unexplained at the molecular level. Here, we present a novel gene, 3-hydroxy-3-methylglutaryl coenzyme A synthase 2 (HMGCS2), encoding a metabolic enzyme in the liver important for energy production from fatty acids, that shows an unusual expression pattern in developing fetal mouse gonads. Shortly after gonadal sex determination it is up-regulated in the developing testes following a very similar spatial and temporal pattern as the male-determining gene Sry in Sertoli cells before switching to ovarian enriched expression.

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There are three human enzymes with HMG-CoA lyase activity that are able to synthesize ketone bodies in different subcellular compartments. The mitochondrial HMG-CoA lyase was the first to be described, and catalyzes the cleavage of 3-hydroxy-3-methylglutaryl CoA to acetoacetate and acetyl-CoA, the common final step in ketogenesis and leucine catabolism. This protein is mainly expressed in the liver and its function is metabolic, since it produces ketone bodies as energetic fuels when glucose levels are low.

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Cornelia de Lange syndrome (CdLS) is an archetypical genetic syndrome that is characterized by intellectual disability, well-defined facial features, upper limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in any one of seven genes, all of which have a structural or regulatory function in the cohesin complex. Although recent advances in next-generation sequencing have improved molecular diagnostics, marked heterogeneity exists in clinical and molecular diagnostic approaches and care practices worldwide.

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Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency (mitochondrial HMG-CoA synthase deficiency or mHS deficiency, OMIM #605911) is an inborn error of metabolism that affects ketone body synthesis. Acute episodes include vomiting, lethargy, hepatomegaly, hypoglycemia and dicarboxylic aciduria. The diagnosis is difficult due to the relatively unspecific clinical and biochemical presentation, and fewer than 30 patients have been described.

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Article Synopsis
  • - The cohesin ring is a vital protein complex made up of four main subunits that plays roles in chromosome segregation, DNA repair, and gene regulation.
  • - The research investigates how the cohesin ring opens by using advanced molecular dynamics simulations and explores the role of ATP hydrolysis in this process.
  • - Findings suggest that the opening of the cohesin ring is a step-by-step process triggered by ATP hydrolysis at one site, which then activates another site, providing insights into related diseases like cohesinopathies and cancer.
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SMC1A encodes one of the proteins of the cohesin complex. SMC1A variants are known to cause a phenotype resembling Cornelia de Lange syndrome (CdLS). Exome sequencing has allowed recognizing SMC1A variants in individuals with encephalopathy with epilepsy who do not resemble CdLS.

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