The utility of whole exome sequencing for identification of the molecular etiology in autosomal recessive developmental and epileptic encephalopathies
Küçük Resim Yok
Tarih
2020
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Springer-Verlag Italia Srl
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
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 inDENDD5A,GRN, andTBCDgenes 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.
Açıklama
Anahtar Kelimeler
Developmental and epileptic encephalopathies, Genetics, Infantile spasms, Mutation, Neonatal seizures
Kaynak
Neurological Sciences
WoS Q Değeri
Q2
Scopus Q Değeri
Q1
Cilt
41
Sayı
12
