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Neurological Sciences

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23.07.2020 | Original Article

The utility of whole exome sequencing for identification of the molecular etiology in autosomal recessive developmental and epileptic encephalopathies

verfasst von: Esra Isik, Sanem Yilmaz, Tahir Atik, Gul Aktan, Huseyin Onay, Sarenur Gokben, Ferda Ozkinay

Erschienen in: Neurological Sciences | Ausgabe 12/2020

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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.

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Titel: The utility of whole exome sequencing for identification of the molecular etiology in autosomal recessive developmental and epileptic encephalopathies
verfasst von: Esra Isik
Sanem Yilmaz
Tahir Atik
Gul Aktan
Huseyin Onay
Sarenur Gokben
Ferda Ozkinay
Publikationsdatum: 23.07.2020
Verlag: Springer International Publishing
Erschienen in: Neurological Sciences / Ausgabe 12/2020
Print ISSN: 1590-1874
Elektronische ISSN: 1590-3478
DOI: https://doi.org/10.1007/s10072-020-04619-8

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