The Genetic Diagnosis of Ultrarare DEEs: An Ongoing Challenge
| Autor: | Luciana Musante, Paola Costa, Caterina Zanus, Flavio Faletra, Flora M. Murru, Anna M. Bianco, Martina La Bianca, Giulia Ragusa, Emmanouil Athanasakis, Adamo P. d’Adamo, Marco Carrozzi, Paolo Gasparini |
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| Přispěvatelé: | Musante, Luciana, Costa, Paola, Zanus, Caterina, Faletra, Flavio, Murru, Flora M., Bianco, Anna M., La Bianca, Martina, Ragusa, Giulia, Athanasakis, Emmanouil, D’Adamo, Adamo P., Carrozzi, Marco, Gasparini, Paolo |
| Rok vydání: | 2022 |
| Předmět: |
neurodevelopmental disorders (NDDs)
epileptic encephalopathies (EEs) developmental and epileptic encephalopathies (DEEs) whole-exome sequencing (WES) reverse phenotyping ndds ees we and epileptic encephalopathies Exome Sequencing Genetics epileptic encephalopathies developmental Humans wes whole-exome sequencing Genetic Testing dees neurodevelopmental disorders Genetics (clinical) Genetic Association Studies Aged ndd epileptic encephalopathie Brain Diseases ee neurodevelopmental disorder Quality of Life and epileptic encephalopathie dee |
| Zdroj: | Genes; Volume 13; Issue 3; Pages: 500 |
| ISSN: | 2073-4425 |
| Popis: | Epileptic encephalopathies (EEs) and developmental and epileptic encephalopathies (DEEs) are a group of severe early-onset neurodevelopmental disorders (NDDs). In recent years, next-generation equencing (NGS) technologies enabled the discovery of numerous genes involved in these conditions. However, more than 50% of patients remained undiagnosed. A major obstacle lies in the high degree of genetic heterogeneity and the wide phenotypic variability that has characterized these disorders. Interpreting a large amount of NGS data is also a crucial challenge. This study describes a dynamic diagnostic procedure used to investigate 17 patients with DEE or EE with previous negative or inconclusive genetic testing by whole-exome sequencing (WES), leading to a definite diagnosis in about 59% of participants. Biallelic mutations caused most of the diagnosed cases (50%), and a pathogenic somatic mutation resulted in 10% of the subjects. The high diagnostic yield reached highlights the relevance of the scientific approach, the importance of the reverse phenotyping strategy, and the involvement of a dedicated multidisciplinary team. The study emphasizes the role of recessive and somatic variants, new genetic mechanisms, and the complexity of genotype–phenotype associations. In older patients, WES results could end invasive diagnostic procedures and allow a more accurate transition. Finally, an early pursued diagnosis is essential for comprehensive care of patients, precision approach, knowledge of prognosis, patient and family planning, and quality of life. |
| Databáze: | OpenAIRE |
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