A5003575342- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- RNA modifications and cancer
- Metabolism and Genetic Disorders
- RNA and protein synthesis mechanisms
- Tumors and Oncological Cases
- Genetic Syndromes and Imprinting
- Health and Medical Education
- Cancer-related gene regulation
- Enzyme Structure and Function
- Genomic variations and chromosomal abnormalities
- Mitochondrial Function and Pathology
- RNA regulation and disease
- Chromosomal and Genetic Variations
- E-Learning and Knowledge Management
- Diet and metabolism studies
- Genomics and Rare Diseases
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Peroxisome Proliferator-Activated Receptors
- Sexual Differentiation and Disorders
- Congenital heart defects research
- Educational Technology in Learning
- Pulmonary Hypertension Research and Treatments
- Epigenetics and DNA Methylation
- Hedgehog Signaling Pathway Studies
Universidad de Zaragoza
2015-2024
Instituto de Investigación Sanitaria Aragón
2017-2024
Biomedical Research Institute of Lleida
2024
Hospital Clínico Universitario Lozano Blesa
2017-2024
Hospital Universitari Arnau de Vilanova
2024
Essen University Hospital
2024
Hospital Universitario Miguel Servet
2024
University of Duisburg-Essen
2024
Pediatrics and Genetics
2024
Vall d'Hebron Institut de Recerca
2024
Cornelia de Lange syndrome (CdLS) is a multisystem genetic disorder with distinct facies, growth failure, intellectual disability, distal limb anomalies, gastrointestinal and neurological disease.Mutations in NIPBL, encoding cohesin regulatory protein, account for >80% of cases typical facies.Mutations the core complex proteins, encoded by SMC1A, SMC3 RAD21 genes, together ∼5% subjects, often atypical CdLS features.Recently, we identified mutations X-linked gene HDAC8 as cause small number...
Cornelia de Lange syndrome (CdLS) is characterized by facial dysmorphism, growth failure, intellectual disability, limb malformations, and multiple organ involvement. Mutations in five genes, encoding subunits of the cohesin complex (SMC1A, SMC3, RAD21) its regulators (NIPBL, HDAC8), account for at least 70% patients with CdLS or CdLS-like phenotypes. To date, only clinical features from a single patient SMC3 mutation has been published. Here, we report efforts an international research...
Characteristic or classic phenotype of Cornelia de Lange syndrome (CdLS) is associated with a recognisable facial pattern. However, the heterogeneity in causal genes and presence overlapping syndromes have made it increasingly difficult to diagnose only by clinical features. DeepGestalt technology, its app Face2Gene, having growing impact on diagnosis management genetic diseases analysing features affected individuals. Here, we performed phenotypic study cohort 49 individuals harbouring...
The NIPBL/MAU2 heterodimer loads cohesin onto chromatin. Mutations in NIPBL account for most cases of the rare developmental disorder Cornelia de Lange syndrome (CdLS). Here we report a MAU2 variant causing CdLS, deletion seven amino acids that impairs interaction between and N terminus. Investigating this interaction, discovered terminus are largely dispensable normal function cells with early truncating mutation. Despite predicted fatal outcome an out-of-frame single nucleotide duplication...
Abstract Cornelia de Lange syndrome (CdLS) manifests facial dysmorphic features, growth and cognitive impairment, limb malformations. Mutations in three genes ( NIPBL , SMC1A SMC3 ) of the cohesin complex its regulators have been found affected patients. Here, we present clinical molecular characterization 30 unrelated patients with CdLS. Eleven had mutations (37%) (10%), giving an overall rate 47%. Several shared same mutation (p.R827GfsX2) but variable phenotypes, indicating influence...
Abstract Cornelia de Lange syndrome (CdLS), Rubinstein–Taybi (RSTS), and KBG are three distinct developmental human disorders. Variants in seven genes belonging to the cohesin pathway, NIPBL , SMC1A SMC3 HDAC8 RAD21 ANKRD11 BRD4 were identified about 80% of patients with CdLS, suggesting that additional causative remain be discovered. Two genes, CREBBP EP300 have been associated RSTS, whereas results from variants . By exome sequencing, a genetic cause was elucidated two clinical diagnosis...
Cornelia de Lange syndrome (CdLS) is a rare disease affecting multiple organs and systems during development. Mutations in the cohesin loader, NIPBL/Scc2, were first described are most frequent clinically diagnosed CdLS patients. The molecular mechanisms driving phenotypes not understood. In addition to its canonical role sister chromatid cohesion, implicated spatial organization of genome. Here, we investigate transcriptome patient-derived primary fibroblasts observe downregulation genes...
DNA double strand breaks (DSBs) are mainly repaired via homologous recombination (HR) or nonhomologous end joining (NHEJ). These pose severe threats to genome integrity but can also be necessary intermediates of normal cellular processes such as immunoglobulin class switch (CSR). During CSR, DSBs produced in the G1 phase cell cycle and by classical NHEJ machinery. By studying B lymphocytes derived from patients with Cornelia de Lange Syndrome, we observed a strong correlation between...
Cornelia de Lange syndrome (CdLS) is a congenital developmental disorder characterized by distinctive craniofacial features, growth retardation, cognitive impairment, limb defects, hirsutism, and multisystem involvement. Mutations in five genes encoding structural components (SMC1A, SMC3, RAD21) or functionally associated factors (NIPBL, HDAC8) of the cohesin complex have been found patients with CdLS. In about 60% patients, mutations NIPBL could be identified. Interestingly, 17% them are...
The cohesin ring is a protein complex composed of four core subunits: Smc1A, Smc3, Rad21 and Stag1/2. It involved in chromosome segregation, DNA repair, chromatin organization transcription regulation. Opening the occurs at "head" structure, formed ATPase domains Smc1A Smc3 Rad21. We investigate mechanisms opening using techniques free molecular dynamics (MD), steered MD quantum mechanics/molecular mechanics (QM/MM MD). study allows thorough analysis events atomic scale: i) ATP hydrolysis...
Abstract Postzygotic mosaicism (PZM) in NIPBL is a strong source of causality for Cornelia de Lange syndrome (CdLS) that can have major clinical implications. Here, we further delineate the role somatic CdLS by describing series 11 unreported patients with mosaic disease-causing variants and performing retrospective cohort study from Spanish diagnostic center. By reviewing literature combining our findings previously published data, demonstrate negative selection against deleterious blood....
El síndrome de Cornelia Lange (SCdL) es una enfermedad rara congénita del desarrollo con afectación multisistémica. Las manifestaciones clínicas son muy variables, pero se distingue entre un fenotipo clásico, caracterizado por unos rasgos craneofaciales distintivos, retraso crecimiento pre y posnatal, defectos reducción las extremidades, hirsutismo discapacidad intelectual, no generalmente más leve difícil diagnosticar. Además, características superponen otros trastornos neurodesarrollo, lo...
Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency (mitochondrial HMG-CoA 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 difficult due to the relatively unspecific clinical biochemical presentation, fewer than 30 patients have been described. This work describes three new with two missense mutations c.334C>T...
3-Hydroxy-3-methylglutaric aciduria is a rare autosomal recessive genetic disorder that affects ketogenesis and L-leucine catabolism. The clinical acute symptoms include vomiting, convulsions, metabolic acidosis, hypoketotic hypoglycaemia lethargy. To date, 33 mutations in 100 patients have been reported the HMGCL gene. In this study 10 new 24 are described. They include: 5 missense mutations: c.109G>A, c.425C>T, c.521G>A, c.575T>C c.598A>T, 2 nonsense c.242G>A c.559G>T, one small deletion:...
Abstract Background Cornelia de Lange syndrome (CdLS) is a dominantly inherited disorder characterized by facial dysmorphism, growth and cognitive impairment, limb malformations multiple organ involvement. Mutations in NIPBL gene account for about 60% of patients with CdLS. This encodes key regulator the Cohesin complex, which controls sister chromatid segregation during both mitosis meiosis. Turner (TS) results from partial or complete absence one X chromosomes, usually associated...
3-Hydroxy-3-methylglutaric aciduria is a rare human autosomal recessive disorder caused by deficiency of 3-hydroxy-3-methylglutaryl CoA lyase (HL). This mitochondrial enzyme catalyzes the common final step leucine degradation and ketogenesis. Acute symptoms include vomiting, seizures lethargy, accompanied metabolic acidosis hypoketotic hypoglycaemia. Such organs as liver, brain, pancreas, heart can also be involved. However, pathophysiology this disease only partially understood. We measured...