Publications by authors named "Edith P Almanza Fuerte"
DNA methylation signatures ("episignatures") can be used as biomarkers of genetic aberrations, clinical phenotypes, and environmental exposures in rare diseases. Episignatures are utilized in molecular diagnostics and can clarify variants of uncertain significance. A growing number of disease genes, including epilepsy genes, exhibit robust and reproducible episignatures.
View Article and Find Full Text PDFArticle Synopsis
- Sequence-based genetic testing finds causative variants in about 50% of cases of developmental and epileptic encephalopathies (DEEs), but DNA methylation changes in these cases have not been thoroughly explored.
- This study analyzed genome-wide DNA methylation in blood samples from 582 individuals with unresolved DEEs, identifying rare methylation patterns and potential genetic causes in 12 of these cases.
- The research highlights the effectiveness of DNA methylation analysis in diagnosing DEEs, showing a 2% diagnostic yield, and provides insights into the CHD2 gene's pathophysiology using advanced sequencing methods.
encodes for the E1 enzyme of the UFMylation cascade, which plays an essential role in ER homeostasis. The clinical phenotypes of UBA5-associated encephalopathy include developmental delays, epilepsy and intellectual disability. To date, there is no humanized neuronal model to study the cellular and molecular consequences of pathogenic variants.
View Article and Find Full Text PDFArticle Synopsis
- Sequence-based genetic testing currently identifies genetic variants in about half of individuals with developmental and epileptic encephalopathies (DEEs), but DNA methylation changes have not been explored in this context.
- This study analyzed genome-wide DNA methylation in blood samples from 516 individuals with unresolved DEEs, uncovering rare methylation changes that helped identify genetic causes in 10 cases.
- The findings suggest that DNA methylation analysis can enhance diagnostic accuracy for DEEs, offering a similar increase in yield to traditional genome sequencing techniques.
Despite widespread clinical genetic testing, many individuals with suspected genetic conditions lack a precise diagnosis, limiting their opportunity to take advantage of state-of-the-art treatments. In some cases, testing reveals difficult-to-evaluate structural differences, candidate variants that do not fully explain the phenotype, single pathogenic variants in recessive disorders, or no variants in genes of interest. Thus, there is a need for better tools to identify a precise genetic diagnosis in individuals when conventional testing approaches have been exhausted.
View Article and Find Full Text PDFArticle Synopsis
- NEXMIF encephalopathy is linked to intellectual disability, autism, and epilepsy, primarily caused by pathogenic variants in the NEXMIF gene.
- The study involved 87 patients (63 females and 24 males) and identified a high prevalence of developmental delays and seizures, particularly in males, who exhibited more severe impairments.
- Key findings show that all identified NEXMIF variants lead to premature stop codons or damaging changes, predominantly occurring de novo, with some cases of somatic mosaicism in affected families.
Lissencephaly (LIS), denoting a "smooth brain," is characterized by the absence of normal cerebral convolutions with abnormalities of cortical thickness. Pathogenic variants in over 20 genes are associated with LIS. The majority of posterior predominant LIS is caused by pathogenic variants in LIS1 (also known as PAFAH1B1), although a significant fraction remains without a known genetic etiology.
View Article and Find Full Text PDF