ABSTRACT
Objective To explore the genetic characteristics in a Chinese family with autosomal dominant lateral temporal lobe epilepsy (ADLTE) and analyze the correlation between genotype and phenotype. Methods The natural history,clinical data and peripheral blood sample were collected in all patients and two healthy members of this ADLTE family.Whole exon sequence(WES)analysis strategy was used to explore the underlying mutations. Possible causative genetic variation was further confirmed by direct PCR and Sanger sequencing. The genotype-phenotype features were compared with previously reported cases. Results A novel pathogenetic LGI1 frameshift mutation p.T134fs was identified in this study. The clinical phenotype was different from reported. Conclusion This study reports a pathogenic LGI1 mutation in a Chinese ADLTE family for the first time, which suggests that LGI1 is a new genetic abnormality of ADLTE in Chinese.
ABSTRACT
Objective To analyze the characteristics of clinical manifestation, brain magnetic resonance imaging ( MRI ) and 18 F-fluoro-deoxy-glucose positron emission tomography ( FDG-PET ) , inflammatory cerebrospinal fluid ( CSF ) , electroencephalography ( EEG ) , and associated tumour in autoimmune epilepsy ( AE) patients with different autoantibodies. Methods Forty-two patients diagnosed as AE with different autoantibodies in Beijing Tiantan Hospital, Capital Medical University between May 2014 and May 2017 were recruited. The clinical manifestation, brain MRI and PET, CSF findings, EEG and biochemical examination of these patients were analyzed. Results Specific autoimmune antibodies were detected in 42 patients, including anti-amphiphysin in one patient, anti-contactin-associated protein 2 in two, anti-γ-aminobutyric acid-B receptor in six, anti-leucine-rich glioma inactivated 1(LGI1) in 24, anti-N-methyl-D-aspartate receptor ( NMDAR ) in nine. The case series of 42 patients had an average age of (49. 9 ± 14. 5) years with a male to female ratio of 5:1. Except anti-NMDAR associated AE, most patients (21/33) presented with the symptoms of limbic encephalitis including temporal lobe seizures, memory decline, personality and neuropsychiatric changes, mesial temporal lobe abnormality in MRI or FDG-PET, and CSF inflammation. The seizure semiologic characteristics included frequent seizure, short seizure duration and common secondarily generalized tonic-clonic seizures during sleeping. Faciobrachial dystonic seizures and hyponatremia were the special clinical manifestation of AE with anti-LGI1. AE patients with all kinds of antibodies presented as initial resistance to anti-epilepsy drugs ( AEDs) and favorable outcome of immunosuppressive treatment in combination with AEDs. Conclusions AE patients with each type of antibody have the special clinical manifestation. Except anti-NMDAR associated AE, the seizure semiologic characteristics often present as frequent and short seizures. All AE patients present as drug refractory epilepsy initially. Seizures in AE patients can be well controlled by immunotherapy combined with AEDs.