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In recent years, as an increasing number of neuronal autoantibodies have been detected and used for clinical diagnosis, clinicians have become more aware of autoimmune encephalitis, causing its reported incidence to trend upward over several years. To date, however, there has been no large-scale epidemiological survey of autoimmune encephalitis in adults and children, and its epidemiological characteristics remain unclear. Six main types of antibodies are detected and used to diagnose autoimmune encephalitis in Chongqing, Southwestern China: anti-NMDA receptor antibody, anti-GABAB receptor antibody, anti-LGI1 antibody, anti-CASPR2 antibody, anti-AMPA1 receptor antibody, and anti-AMPA2 receptor antibody. From January 2012 to February 2018, 189 patients at six general hospitals in Chongqing were diagnosed with autoimmune encephalitis and were positive for neuronal autoantibodies. In this report, the epidemic situation and the antibody distribution among these patients are analyzed and described in detail. The differences in disease severity among different ages and between the sexes are evaluated, and the correlation between antibody titer and disease severity is also assessed.

Rationale: Early infantile epileptic encephalopathy (EIEE) 65 was recently shown to be caused by the cytoplasmic FMRP interacting protein 2 (CYFIP2) mutation. To date, only 5 cases have been reported in two articles, and all the outcomes in all cases were poor.Patient concerns: In this study, we reported an 8-month-old girl with a 1 month-long history of seizures and developmental delay. Over 1 month later, she developed epileptic spasms in clusters with hypsarrhythmia on electroencephalography. Diagnosis:The patient was diagnosed with EIEE 65 and trio-based whole-exome sequencing revealed a causative de novo CYFIP2 mutation c.260G >T (p.Arg87Leu). Interventions:The proband was successively treated with multiple antiepileptic drugs, including levetiracetam, phenobarbital, VitB6, topiramate, methylprednisolone, prednisone, valproic acid and vigabatrin.Outcomes: After resistance to multiple anti-epileptic drugs over 2 months of treatment, she finally achieved seizure-free several days after vigabatrin administration and her developmental delay steadily improved.Lessons: Our case confirmed that CYFIP2 was the pathogenic gene of EIEE 65. We also first demonstrated vigabatrin might be effective for control of seizures and helpful for the improved outcomes of these patients.Abbreviations: CYFIP2 = cytoplasmic FMRP interacting protein 2, EE = epileptic encephalopathy, EEG = electroencephalography, EIEE = early infantile epileptic encephalopathy, GTCSs = generalized tonic-clonic seizures, MRI = magnetic resonance imaging, SD = standard deviation, WAVE = WASP-family verprolin-homologous protein, WES = whole-exome sequencing.

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This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. AbstractBackground: VAC14 is a component of a trimolecular complex that tightly regulates the level of phosphatidylinositol 3,5-bisphosphate [PI (3,5) P2]. VAC14 pathogenic variants cause prominent vacuolation of neurons in basal ganglia of patients with childhood-onset striatonigral degeneration (SNDC). Methods: We identified two siblings with SNDC. Whole-exome sequencing was performed for genetic molecular analysis in these probands. Results: The patients were compound heterozygotes for two novel variants in the VAC14 gene, p.Ala582Thr and p.Arg681His. The pathogenicity of these variants was indicated by a bioinformatic study and protein three-dimensional modeling.Eight previously reported SNDC cases and a Yunis-Varón syndrome caused by VAC14 mutations were summarized and compared. Conclusion: We present novel compound heterozygous variants (c.1744G>A/ c.2042G>A) in our proband, and these novel variants were predicted to be likely pathogenic. The affected siblings were clinically severe and lethal; their phenotypes were similar to the majority of previously reported SNDC cases, with the exception of two cases that showed mild clinical manifestations. VAC14 pathogenic variants may be associated with various phenotypes. Herein, we report the Chinese siblings with SNDC, they are the first Asian cases. Our results expanded the spectrum of VAC14 pathogenic variants and the ethnic backgrounds of the affected cases. K E Y W O R D Sbasal ganglia, striatonigral degeneration, VAC14, variant, whole-exome sequencing SUPPORTING INFORMATIONAdditional supporting information may be found online in the Supporting Information section.

To the best of our knowledge, the present study reported the case of the first Chinese patient with microcephaly-capillary malformation (MIC-CAP) syndrome caused by a novel compound heterozygous mutation in the STAMBP gene, which encodes STAM binding protein. The present study also provides a review of relevant previously published studies. A boy with MIC-CAP syndrome with developmental delay, intractable epilepsy and prominent dyskinesia was examined. A pathogenic mutation was identified by whole-exome sequencing, and the protein structure and function affected by this mutation were predicted using bioinformatics analysis. Finally, the clinical features of 16 other cases reported in previous studies were reviewed and compared. A novel compound heterozygous mutation of the STAMBP (c.1119-1G>T, c.968A>G) was identified in the present study and epilepsy was refractory, consistent with previously reported cases. The present study also highlighted the fact that STAMBP mutation-associated MIC-CAP often presents as intractable early-life epilepsy, which may lead to mortality.

Temtamy syndrome is an extremely rare disorder caused by chromosome 12 open reading frame 57 (C12orf57) pathogenic variants. The present study reported a boy with Temtamy syndrome displaying global developmental delay, epilepsy and dysmorphic facial appearance. Whole-exome sequencing was performed to identify a novel homozygous pathogenic variant of C12orf57 (c.3G >C, p.Met1IIe), and the affected protein structure and function were predicted to be pathogenic. Additionally, clinical features of the other reported 56 patients with C12orf57 pathogenic variants were reviewed and compared. This study highlighted that C12orf57 pathogenic variants are mainly associated with global developmental delay, epilepsy and dysmorphic facial appearances. The clinical features were in accordance with the previously reported cases, except for those with recurrent infection, but without corpus callosum abnormalities. The present study reported the first Asian case to the best of our knowledge with Temtamy syndrome, and the novel C12orf57 pathogenic variant has not reported in any ethnic groups previously. The present study expanded the spectrum of C12orf57 pathogenic variants as well as the ethnic backgrounds of the affected patients.

Coffin-Siris syndrome1 (CSS1; Online Mendelian Inheritance in Man no. 135900) is a multiple malformation syndrome characterized by intellectual and/or developmental delay, and hypoplastic or absent fifth fingernails and/or toenails. AT-rich interaction domain-containing protein 1B (ARID1B) is the most frequently mutated gene in CSS1 and the majority of reported cases have been sporadic. Using whole-exome sequencing, the present study identified two siblings with CSS1 with a novel heterozygous co-segregating pathogenic variant in the ARID1B gene (c.3468_3471del). Additionally, the current study confirmed a 4% somatic ARID1B mosaicism in the patient's mother. The results expanded the spectrum of known ARID1B pathogenic variants. To the best of our knowledge, the present study is the first to provide experimental evidence that an ARID1B pathogenic variant can be inherited from a clinically healthy somatogonadal mosaic mother.