Back to Search
Start Over
Seizure / Compound heterozygous SZT2 mutations in two siblings with early-onset epilepsy, intellectual disability and macrocephaly
- Publication Year :
- 2019
- Publisher :
- Elsevier, 2019.
-
Abstract
- Purpose Mutations in SZT2 have been previously reported in several cases of early onset epilepsy and intellectual disability. In this study we investigate potential causal mutations in two male siblings affected by early onset epilepsy, intellectual disability and macrocephaly. Methods We use family-based whole-exome sequencing to identify candidate variants. Results We report the identification of two potential causal SZT2 mutations in compound heterozygous state. We observe considerable differences in the clinical phenotype severity of the two affected individuals. The cerebral MRI revealed no abnormalities in the older affected brother, while in the youngest one it revealed a right frontal polymicrogiria. Moreover, while good seizure control was achieved in the older affected individual the younger brother is affected by pharmacoresistant epilepsy, progressive spastic paraplegia, cortical myoclonus and a more severe intellectual disability. We also analyzed the relative location of the reported pathogenic mutations in the SZT2 protein. Conclusion Variable phenotypic expressivity is observed for this condition, while the location and type of mutations in SZT2 also has a potential impact on epilepsy severity. These findings extend our knowledge of epileptogenic conditions related to SZT2 and mTOR signaling.
- Subjects :
- Adult
Male
Pediatrics
medicine.medical_specialty
Epileptic and developmental encephalopathies
DNA Mutational Analysis
Intellectual disability
Nerve Tissue Proteins
Compound heterozygosity
03 medical and health sciences
Epilepsy
Young Adult
0302 clinical medicine
Intellectual Disability
Exome Sequencing
medicine
Humans
Expressivity (genetics)
Longitudinal Studies
Young adult
Exome sequencing
Family Health
business.industry
Macrocephaly
Whole exome sequencing
General Medicine
medicine.disease
Phenotype
Magnetic Resonance Imaging
Megalencephaly
Neurology
Mutation
SZT2
Neurology (clinical)
mTORopathies
medicine.symptom
business
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....f6f207dd0845127c31e2b6a3465469c9