The utility of whole exome sequencing for identification of the molecular etiology in autosomal recessive developmental
- PDF / 1,022,371 Bytes
- 11 Pages / 595.276 x 790.866 pts Page_size
- 67 Downloads / 177 Views
ORIGINAL ARTICLE
The utility of whole exome sequencing for identification of the molecular etiology in autosomal recessive developmental and epileptic encephalopathies Esra Isik 1
&
Sanem Yilmaz 2 & Tahir Atik 1 & Gul Aktan 2 & Huseyin Onay 3 & Sarenur Gokben 2 & Ferda Ozkinay 1,3
Received: 11 April 2020 / Accepted: 19 July 2020 # Fondazione Società Italiana di Neurologia 2020
Abstract Aim Developmental and epileptic encephalopathies (DEEs) are a group of devastating disorders caused by epileptic activity, resulting in deterioration in developmental, cognitive, and motor functions. The number of genes identified as being responsible for DEEs has been increasing rapidly. However, despite a comprehensive molecular analysis, a molecular diagnosis can only be established in 50% of cases. The aim of this project is to use whole exome sequencing (WES) to determine the molecular etiology of DEEs in undiagnosed patients with a pedigree suggestive of an autosomal recessive single gene disease. Methods Three DEE families, having either consanguineous parents of an affected individual and/or having more than one affected offspring, were enrolled in the project. Prior to this project, the families had been evaluated using a next-generation sequencing panel including 16 DEE genes in a previous study; however, no molecular diagnosis could be established. In five cases from the three selected DEEs families in our study, the genetic etiology was investigated using WES. Results All patients in the study group had infantile onset epileptic seizures; however, semiologies varied. All patients presented with severe developmental delay. WES revealed biallelic disease causing mutations in DENDD5A, GRN, and TBCD genes in family 1, family 2, and family 3, respectively. In each family, the identified variants associated with the disease were segregated. Reverse phenotyping supported the molecular analysis. Conclusion This study provided a valuable contribution to the genotype-phenotype relationship by determining rare epilepsy syndromes in undiagnosed patients previously. WES is a useful diagnostic alternative, particularly in consanguineous families. Keywords Developmental and epileptic encephalopathies . Genetics . Infantile spasms . Mutation . Neonatal seizures
Introduction Developmental and epileptic encephalopathies (DEEs) are a group of devastating disorders caused by epileptic activities, resulting in deterioration in developmental, cognitive, and motor functions [1, 2]. Early-onset epileptic encephalopathies appear during neonatal and infantile period. DEEs are a
* Esra Isik [email protected] 1
Subdivision of Pediatric Genetics, Department of Pediatrics, Faculty of Medicine, Ege University, Bornova, Izmir, Turkey
2
Subdivision of Child Neurology, Department of Pediatrics, Faculty of Medicine, Ege University, Izmir, Turkey
3
Department of Medical Genetics, Faculty of Medicine, Ege University, Izmir, Turkey
heterogeneous group of disorders resulted by congenital or acquired cerebral damage. The number of genes which b
Data Loading...
