Analysis of Salt Stress on Soil Microbial Community Composition and Its Correlation with Active Components in the Rhizosphere of Acanthopanax senticosus.

Salt stress can adversely affect plant seed germination, growth and development, and eventually lead to slow growth and even death of plants. The purpose of this study was to investigate the effects of different concentrations of NaCl and Na2SO4 stress on the physicochemical properties, enzyme activities, rhizosphere microbial community and seven active components (L-phenylalanine, Protocatechuic acid, Eleutheroside B, Chlorogenic acid, Caffeic acid, Eleutheroside E, Isofraxidin) of Acanthopanax senticosus rhizosphere soil. Statistical analysis was used to explore the correlation between the rhizosphere ecological factors of Acanthopanax senticosus and its active components. Compared with Acanthopanax senticosus under NaCl stress, Na2SO4 generally had a greater effect on Acanthopanax senticosus, which reduced the richness of fungi in rhizosphere soil and adversely affected the content of multiple active components. Pearson analysis showed that pH, organic matter, ammonium nitrogen, available phosphorus, available potassium, catalase and urease were significantly correlated with active components such as Caffeic acid and Isofraxidin. There were 11 known bacterial genera, 12 unknown bacterial genera, 9 known fungal genera and 1 unknown fungal genus significantly associated with the active ingredient. Salt stress had great changes in the physicochemical properties, enzyme activities and microorganisms of the rhizosphere soil of Acanthopanax senticosus. In conclusion, different types and concentrations of salts had different effects on Acanthopanax senticosus, and the active components of Acanthopanax senticosus were regulated by rhizosphere soil ecological factors.

Deep brain stimulation for pediatric pantothenate kinase-associated neurodegeneration with status dystonicus: A case report and literature review.

BACKGROUND: Pantothenate kinase-associated neurodegeneration (PKAN) is a type of inherited metabolic disorder caused by mutation in the PANK2 gene. The metabolic disorder mainly affects the basal ganglia region and eventually manifests as dystonia. For patients of dystonia, their dystonic symptom may progress to life-threatening emergency--status dystonicus. OBJECTIVE: We described a case of a child with PKAN who had developed status dystonicus and was successfully treated with deep brain stimulation (DBS). Based on this rare condition, we analysed the clinical features of PKAN with status dystonicus and reviewed the reasonable management process of this condition. CONCLUSION: This case confirmed the rationality of choosing DBS for the treatment of status dystonicus. Meanwhile, we found that children with classic PKAN have a cluster of risk factors for developing status dystonicus. Once children diagnosed with similar neurodegenerative diseases are under status dystonicus, DBS can be active considered because it has showed high control rate of this emergent condition.

Encephalitis is an Important Phenotype of Myelin Oligodendrocyte Glycoprotein Antibody-Associated Diseases: A Single-Center Cohort Study.

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is considered a demyelinating disease of the central nervous system, but an increasing number of encephalitis cases associated with MOG antibodies have been reported recently. METHODS: This was a single-center, retrospective study. All data for pediatric patients with MOGAD diagnosed at Beijing Children's Hospital from January 2017 to January 2022 were collected. Clinical characteristics and outcomes were analyzed, and treatment responses were compared between the rituximab (RTX) and mycophenolate mofetil (MMF) groups. RESULTS: A total of 190 patients (age range: 5 months to 16 years; median age: 7.2 years; females: 97) were included in this study. The phenotypes of the first attack included acquired demyelinating syndromes (105 [55%]), encephalitis other than acute disseminated encephalomyelitis (82 [43%]), and isolated meningitis (3 [2%]). After a median follow-up of 30.4 months (interquartile range: 14.8-43.7), 64 (34%) patients had relapses. Fifty-one of the 64 (80%) patients who had relapse received maintenance therapy, including MMF (41), RTX (11), maintenance intravenous immunoglobulin (two), and tocilizumab (two). The annualized relapse rates decreased significantly after treatment in both the RTX and MMF cohorts (P < 0.05); however, there were no significant differences between the two groups (P = 0.56). A total of 178 (94%) patients had complete (175 patients) or almost complete (three patients) recovery (modified Rankin scale [mRS] < 2), and 12 had moderate to severe deficits (mRS ≥ 2). CONCLUSIONS: The spectrum of pediatric MOGAD is broader than previously reported and includes demyelinating syndromes and encephalitis. Encephalitis is an important initial phenotype observed in pediatric patients with MOGAD.

A new phenotype of EVEN-PLUS syndrome in a Chinese family and literature review.

BACKGROUND: Epiphyseal, Vertebral, Ear, and Nose (EVEN)-PLUS syndrome is a rare condition characterized by the involvement of the Epiphyses, Vertebrae, Ears, and Nose, plus other associated findings, due to pathogenic variants in the HSPA9 gene. Due to the sparse number of patients, the clinical phenotypic spectrum is not clear. METHODS: We report two patients with pathogenic HSPA9 variants from a Chinese family. Besides the core clinical features of EVEN-PLUS syndrome, the two cases had seizures, developmental delay, and basal ganglia lesions in cerebral MRI. We also reviewed the previously published reports of patients with biallelic pathogenic HSPA9 variants. RESULTS: Together with the presented cases, 12 cases (9 females) were identified from 6 relevant research items for analysis. All patients had synophrys or arched eyebrows, hypoplastic or dysplastic ears, hypoplastic nasal bone, and dysplastic femoral head. Other specific craniofacial features (such as triangular nares), abnormal skeletal presentations (such as bifid femur, dysplastic epiphyses at the knee, dysplastic acetabula, delayed ossification, short stature, vertebral clefting, scoliosis, and dislocated patellae), congenital heart defects, and renal alterations are common clinical features. Two patients had seizures and basal ganglia lesions in cerebral MRI. Infrequent features, such as aplasia cutis, short thorax and sternum, and widely spaced nipples, are also observed in the syndrome. Thirteen variants associated with EVEN-PLUS syndrome have been reported. CONCLUSIONS: HSPA9 gene mutations should be suspected in all cases with specific craniofacial features, abnormal skeletal presentations, congenital heart defects, and renal alterations. Seizures and basal ganglia lesions are a new phenotype of EVEN-PLUS syndrome.

[Electroencephalogram characteristics of 26 children with febrile infection-related epilepsy syndrome]. / 26ä¾‹å„¿ç«¥å‘çƒ­æ„ŸæŸ“ç›¸å ³æ€§ç™«ç—«ç»¼åˆå¾çš„è„‘ç”µå›¾åˆ†æž.

OBJECTIVES: To investigate the electroencephalogram (EEG) characteristics and progression of febrile infection-related epilepsy syndrome (FIRES) in children, aiming to enhance diagnosis and treatment approaches. METHODS: A retrospective analysis was conducted on 26 children with FIRES between May 2017 and December 2021. RESULTS: All 26 children (100%) presented with fever at the onset, followed by frequent convulsions that rapidly progressed into convulsive status. Ventilator support was required for 22 cases (85%). During the acute phase, EEG features demonstrated the disappearance of background activity and physiological sleep cycles in all children. Diffuse slow waves and multifocal slow spike slow waves were observed as abnormal waves during the interictal period. A characteristic pattern of focal low amplitude fast wave initiation was detected in all children during seizure episodes. In the chronic phase, the background EEG activity gradually recovered, and the presence of abnormal waves was relatively limited. The characteristic pattern of focal slow wave rhythm initiation was evident during seizure episodes. Additionally, extreme δ brushes were observed in four cases (15%). CONCLUSIONS: These findings suggest that EEG manifestations in children with FIRES exhibit distinctive patterns during the acute and chronic stages, providing significant value for early diagnosis and clinical staging. Extreme δ brushes may be one of the distinctive markers of children with FIRES.

The clinical spectrum associated with ATP1A2 variants in Chinese pediatric patients.

PURPOSE: To evaluate the clinical spectrum associated with ATP1A2 variants in Chinese children with hemiplegia, migraines, encephalopathy or seizures. METHODS: Sixteen children (12 males and 4 females), including ten patients with ATP1A2 variants whose cases had been published previously, were identified using next-generation sequencing. RESULTS: Fifteen patients had FHM2 (familial hemiplegic migraine type 2), including three who had AHC (alternating hemiplegia of childhood) and one who had drug-resistant focal epilepsy. Thirteen patients had DD (developmental delay). The onset of febrile seizures, which occurred between 5 months and 2 years 5 months (median 1 year 3 months) was earlier than the onset of HM (hemiplegic migraine), which occurred between 1 year 5 months and 13 years (median 3 years 11 months). Disturbance of consciousness subsided first, at 40 h to 9 days (median 4.5 days); hemiplegia and aphasia were resolved slowly, taking 30 min to 6 months (median 17.5 days) for the former and 24 h to over 1 year (median 14.5 days) for the latter. Cranial MRI showed edema in the cerebral hemispheres, mainly the left hemisphereacute attacks. All thirteen FHM2 patients recovered to baseline in 30 min to 6 months. Fifteen patients had between 1 and 7 (median 2) total attacks between the baseline and follow-up timepoints. We report twelve missense variants, including a novel variant ATP1A2 variant, p.G855E. CONCLUSIONS: The known genotypic and phenotypic spectra of Chinese patients with ATP1A2-related disorders were further expanded. Recurrent febrile seizures and DD combined with paroxysmal hemiplegia and encephalopathy should raise the clinical suspicion of FHM2. The avoidance of triggers and thus the prevention of attacks may be the most effective therapy for FHM2.

Basal nuclei lesions and cholecystitis as initial findings of late infantile metachromatic leukodystrophy.

Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal disease. MLD can be divided into three clinical forms: late infantile, juvenile, and adult, with late infantile being the most common. Infantile MLD with unusual onset has been reported. In the study, we reported a case of late infantile MLD with basal nuclei lesions and cholecystitis as the initial findings, which further broadens late infantile MLD onset and contributes to early clinical diagnosis.

Clinical and genetic spectrum of hereditary spastic paraplegia in Chinese children.

AIM: To explore the clinical and genetic spectrum of hereditary spastic paraplegia (HSP) in Chinese children. METHOD: This retrospective study was conducted between January 2014 and October 2021 in children clinically diagnosed with either pure HSP (pHSP) or complex HSP (cHSP). RESULTS: We investigated 45 children (32 males, 13 females; mean age [SD] at symptom onset 4 years [7 months]). clinically diagnosed with HSP and identified genetic causes in 35 patients. Most patients with autosomal dominant HSP had pHSP (16/18), whereas most patients with autosomal recessive HSP tended to have cHSP (14/16). SPG11 was the most common autosomal recessive subtype, followed by FA2H/SPG35, whereas SPAST/SPG4 was the most frequent cause of autosomal dominant HSP. Two patients with CPT1C mutations presented with a complex phenotype. Meanwhile, 10 patients were found to have likely pathogenic variants/variants of uncertain clinical significance in six genes related to HSP. INTERPRETATION: SPG11 and SPG4 were the most frequent subtypes in Chinese children with autosomal recessive HSP and autosomal dominant HSP. However, the prevalence of SPG4 was much lower than that in adults, which might be explained by the late onset of the disease. On the other hand, FA2H/SPG35 was common in our cohort, while it contributed to only a small proportion of adult cases, which might be explained by its rapid progression and early death in some patients. We also expanded the genetic and clinical spectra of SPG73.

Mycophenolate mofetil: An alternative disease-modifying agent for MOG-IgG-associated disorders in childhood: A single-center bidirectional cohort study.

OBJECTIVE: To evaluate the efficacy of mycophenolate mofetil (MMF) in the treatment of childhood MOG-IgG-associated disorder (MOGAD). METHODS: Thirty patients diagnosed with relapsing MOGAD and treated with MMF for >1 year from a childhood MOGAD ambispective cohort were included in the study. The clinical characteristics, therapeutic regimen, side effects, annualized relapse rate (ARR), and Expanded Disability Status Scale (EDSS) scores of these patients were evaluated. RESULTS: The median age of disease onset was 7.05 (2.50-12.75) years. The male to female ratio was 1:1.31. All patients used MMF as first-line maintenance treatment. The median time to add MMF from disease onset was 1.08 (0.25-5.00) year. The median number of attacks before MMF initiation was 2 (2 - 8). The median duration of MMF therapy was 2.13 (1.00-3.58) years. Twenty (66.67%) patients did not experience further attacks during MMF therapy. The Kaplan-Meier curves showed a 3-year relapse-free rate of 59.8% (95% CI, 36.62-76.88%). ARR decreased during MMF therapy (0 (0 - 1.72) vs. 1.25 (0.60-4.00); P < 0.05). EDSS stabilized during MMF therapy (1.0 (0 - 2.0) vs. 0 (0 - 2.0); P = 0.206). None of the patients stopped the use of MMF due to intolerable side effects. Onset age, sex, phenotype of the first attack, ARR before MMF, MOG-IgG titers, and combined long-term prednisone (prednisone <10 mg daily for patients >40 kg or <5 mg daily for patients ≤40 kg longer than 6 months) did not predict recurrence during MMF therapy in univariate analysis. CONCLUSIONS: MMF was effective and safe for treating childhood MOGAD. No clinical feature that could predict efficacy of MMF was found in pediatric patients with MOGAD.

Oculogyric crisis mimicked epilepsy in a Chinese aromatic L-amino acid decarboxylase-deficiency patient: A case report.

Background: Aromatic amino acid decarboxylase (AADC) deficiency is a rare, autosomal recessive neurometabolic disorder with heterogeneous phenotype, including hypotonia, movement disorders, autonomic dysfunction, and developmental delay. Here, we reported a Chinese patient with AADCD who was initially misdiagnosed with epilepsy. Case presentation: The proband was a 4-month-old Chinese girl, representing hypotonia, episodes of oculogyric crises with dystonia, and delayed developmental milestones. The patient was first misdiagnosed with epilepsy because of the similarity between episodes of oculogyric crisis and epileptic seizure. The accurate diagnosis of AADCD was established through analysis of neurotransmitters in cerebrospinal fluid (CSF). The genetic test confirmed the patient carried novel compound heterozygous mutations in the DDC gene:c.419G>A and c.1375C>T. Conclusion: This study reported a patient with AADCD who was initially misdiagnosed as epilepsy. Two novel missense mutations in the DDC gene were identified from the patient and her family. Little infants with epileptic-like attacks should consider AADCD. An accurate diagnosis of AADCD is essential for drug choice and patient management.

Functional connectivity differences in speech production networks in Chinese children with Rolandic epilepsy.

Previous studies have demonstrated that language impairments are frequently observed in patients with benign epilepsy with centrotemporal spikes (BECTS). However, how BECTS affects language processing in the Chinese population remains unclear. With the use of functional magnetic resonance imaging (fMRI) in an overt picture-naming task, the present study examined functional connectivity in 27 children with BECTS and 26 healthy controls. The results indicated that children with BECTS showed altered functional connectivity associated with speech production between the left precuneus and the right cerebellum, between the right precuneus and the bilateral thalamus and the left superior temporal gyrus, between the right cuneus and the right postcentral gyrus and the right inferior parietal lobule, and between the right cerebellum and right middle frontal gyrus. Collectively, the findings in this study demonstrate the abnormal functional connectivity basis of speech production in Chinese children with BECTS, providing clues to understanding the brain mechanisms of language-related network in patients with BECTS.

Transcriptomic analysis reveals the mechanism of host growth promotion by endophytic fungus of Rumex gmelinii Turcz.

Rumex gmelinii Turcz. (RGT) is a medicinal plant of the genus Rumex, family Polygonaceae. Our research group isolated an endophytic fungus, Plectosphaerella cucumerina (Strain J-G) from RGT, which could significantly promote host growth when co-cultured with host seedlings. In this study, we used transcriptome analysis and verification experiments to explore the molecular mechanisms underlying this growth-promoting effect. We found that, during co-culture with Strain J-G, the expression of genes encoding key enzymes in amino acid metabolism and carbohydrate synthesis and metabolism were up-regulated in RGT tissue culture seedlings, providing additional substrate and energy for plant growth. In addition, the expression of genes encoding the responser of RGT seedlings to hormones, including auxin and cytokinin, were significantly enhanced, promoting plant growth and development. Furthermore, RGT seedling defense systems were mobilized by Strain J-G; therefore, more secondary metabolites and substances involved in stress resistance were produced, ensuring normal plant growth and metabolism. The research showed Strain J-G significantly promote the accumulation of biomass and effective components of RGT, which provide basis for its application. This research also provides a reference method for the study of growth-promoting mechanism of endophytic fungi.

Novel Loss-of-Function Variants in CHD2 Cause Childhood-Onset Epileptic Encephalopathy in Chinese Patients.

Developmental and epileptic encephalopathy-94 (DEE94) is a severe form of epilepsy characterized by a broad spectrum of neurodevelopmental disorders. It is caused by pathogenic CHD2 variants. While only a few pathogenic CHD2 variants have been reported with detailed clinical phenotypes, most of which lack molecular analysis. In this study, next-generation sequencing (NGS) was performed to identify likely pathogenic CHD2 variants in patients with epilepsy. Three likely pathogenic variants were finally identified in different patients. The seizure onset ages were from two years to six years. Patients 1 and 2 had developmental delays before epilepsy, while patient 3 had intellectual regression after the first seizure onset. The observed seizures were myoclonic, febrile, and generalized tonic-clonic, which had been controlled by different combinations of antiepileptic drugs. Two de novo (c.1809_1809+1delGGinsTT, p.? and c.3455+2_3455+3insTG, p.?) and one maternal (c.3783G>A, p.W1261*) variant were identified, which were all predicted to be pathogenic/likely pathogenic. Molecular analysis was performed in patient 1, and we detected aberrantly spliced products, proving the pathogenicity of this CHD2 variant. New cases with novel variants, along with a detailed clinical and molecular analysis, are important for a better understanding of CHD2-related epileptic encephalopathy.

Multisource Deep Transfer Learning Based on Balanced Distribution Adaptation.

The current traditional unsupervised transfer learning assumes that the sample is collected from a single domain. From the aspect of practical application, the sample from a single-source domain is often not enough. In most cases, we usually collect labeled data from multiple domains. In recent years, multisource unsupervised transfer learning with deep learning has focused on aligning in the common feature space and then seeking to minimize the distribution difference between the source and target domains, such as marginal distribution, conditional distribution, or both. Moreover, conditional distribution and marginal distribution are often treated equally, which will lead to poor performance in practical applications. The existing algorithms that consider balanced distribution are often based on a single-source domain. To solve the above-mentioned problems, we propose a multisource transfer learning algorithm based on distribution adaptation. This algorithm considers adjusting the weights of two distributions to solve the problem of distribution adaptation in multisource transfer learning. A large number of experiments have shown that our method MTLBDA has achieved significant results in popular image classification datasets such as Office-31.

Analysis of the mechanism of saponin biotransformation in Dioscoreae nipponicae rhizoma by the endophytic fungus Fusarium sp. C39 using whole-genome sequencing.

Fusarium sp. C39 is an endophytic fungus of Dioscorea nipponica Makino. Symbiosis of Fusarium sp. C39 with Rhizoma Dioscoreae Nipponicae (RDN) can significantly increase the content of saponin, which provides a new approach for saponin production and reduces the pressure on natural sources of saponins. However, the underlying mechanism is not clear, limiting its application. In this study, the genome of Fusarium sp. C39 was sequenced, the gene functions were predicted via gene annotation, and the genome was compared to the genomes of four related species. Fusarium sp. C39 is predicted to encode many key enzyme genes involved in saponin synthesis, which could transform the mevalonate, isopentenyl pyrophosphate, and various intermediate compounds present in the RDN extract into saponins. The Fusarium sp. C39 genome contains specific genes that are conducive to its endophytic lifestyle and can provide abundant raw materials for saponin synthesis. Based on the genomic analysis, we proposed the mechanism by which Fusarium sp. C39 generates saponins and provides a theoretical basis for rapid, efficient, low-cost production of saponins.

Chinese patients with p.Arg756 mutations of ATP1A3: Clinical manifestations, treatment, and follow-up.

Importance: The phenotypes of ATP1A3 gene mutations are diverse. Relapsing encephalopathy with cerebellar ataxia and fever-induced paroxysmal weakness and encephalopathy (FIPWE) are considered non-classical phenotypes caused by p.Arg756 mutations of ATP1A3. Objective: To summarize the clinical manifestations, treatment, and follow-up of Chinese patients with p.Arg756 mutations of ATP1A3. Methods: We analyzed the clinical features, treatment, and genotypes of eight children with p.Arg756 mutations of ATP1A3 who were treated in Beijing Children's Hospital from January 2014 to December 2019. Results: Eight patients (six boys and two girls) were included; seven had been misdiagnosed with encephalitis. The age of onset ranged from 0.8 to 4.5 years. All patients had encephalopathy and had at least one episode of FIPWE. Cerebellar ataxia was present in nine episodes. Reversible splenial lesions of the corpus callosum were found in two patients in the acute phase. Three types of heterozygous ATP1A3 mutations were found: c.2267G > T (p.R756L) (patient 3 [P3]), c.2266C > T (p.R756C) (P2 and P4), and c.2267G > A (p.R756H) (P1, P5, P6, P7, and P8). Six mutations were de novo; two mutations were inherited. Both patients with p.R756C and one patient (P7) with p.R756H had four episodes of severe ataxia as the main manifestations. However, in the other three episodes, limb weakness was more prominent than ataxia. P5 with p.R756H exhibited overlap with FIPWE and rapid-onset dystonia-parkinsonism. Interpretation: Acute encephalopathy followed by febrile disease was characteristic of the disease in patients with p.Arg756 mutations of ATP1A3. However, the weakness and ataxia were variable. Phenotypic crossover and overlap were observed among these patients.

Expanding the mutational spectrum of Rahman syndrome: A rare disorder with severe intellectual disability and particular facial features in two Chinese patients.

BACKGROUND: The study aimed to investigate the clinical and genetic features of Rahman syndrome caused by HIST1H1E gene mutations. METHODS: We retrospectively analyzed the clinical information and genetic testing results of a Rahman syndrome family in an outpatient clinic in August 2020 and summarized the clinical characteristics of the HIST1H1E gene mutations in conjunction with peer-reviewed reports. RESULTS: A 4-year-old boy was diagnosed with severe developmental delay and with specific features (large head, full cheeks, high hairline, low-set ear, sparse eyebrows, and short neck) similar to his mother (mild intellectual disability, high hairline, reduced hair, ptosis, sagging skin, and hyperkeratosis) and premature aging. Trio whole exome sequencing (WES) revealed a novel maternal c.368dup (p.G124Rfs*72) heterozygous mutation in the HIST1H1E gene. There have been only a few reported cases with mainly de novo mutations. Only six peer-reviewed articles in English and one in Chinese have been published regarding this syndrome. From 48 children with Rahman syndrome, 21 were males and 27 were females encompassing 25 mutations in the HIST1H1E gene. All mutations located in C-terminal tail were frameshift mutations leading to premature protein termination. CONCLUSION: Rahman syndrome, caused by the HIST1H1E gene mutation, is a rare autosomal dominant disorder in which the patient has an unusual facial appearance with high hairline and full cheeks, and clinical manifestations of mild to severe intellectual disability, motor delay and speech delay. Genetic testing may assist in the diagnosis of these patients. This diagnosis will permit early speech rehabilitation to improve their quality of life.

Leigh Syndrome: A Study of 209 Patients at the Beijing Children's Hospital.

OBJECTIVE: Leigh syndrome (LS) is a heterogeneous neurodegenerative disease and the most frequent pediatric manifestation of mitochondrial disease. In the largest patient collection to date, this study aimed to provide new insights into the clinical and genetic spectrum of LS, defect-specific associations, and predictors of disease course and survival. METHODS: Clinical, metabolic, neuroimaging, onset, and survival data were collected from the medical records of 209 patients referred to the Beijing Children's Hospital with symmetrical basal ganglia and/or brainstem neuroimaging changes indicative of LS by 30 centers from the Chinese network of mitochondrial disease (mitoC-NET) between January 2013 and July 2021 for exploratory analysis. RESULTS: Pathogenic variants were identified in 52 genes, most frequently MT-ATP6, SURF1, and PDHA1. Maternally inherited variants accounted for 42% (heteroplasmy level ≥90% in 64%). Phenotypes spanned 92 Human Phenotype Ontology terms. Elevated serum lactate (144/195), global developmental delay (142/209), and developmental regression (103/209) were most frequent. Discriminating neuroimaging and/or clinical features were identified for MT-ATP6 (m.9176T>C), MT-ND5, PDHA1, SUCLG1, and SURF1. Poorest survival was associated with MT-ND5, MT-ATP6 (m.8993T>C and m.9176T>C), SURF1, and ALDH5A1 (≤50% 3 year's survival), in contrast to milder defects with specific treatment (ECHS1 and SLC19A3, 100% 3 year's survival). INTERPRETATION: Our data define phenotype, onset, and survival of LS in a defect-specific manner, identifying features discriminating between genetic defects and predictive of disease outcome. These findings are essential to early diagnosis, in optimizing family counseling, and to the design and monitoring of future clinical trials, the next frontier of LS research. ANN NEUROL 2022;91:466-482.

Genotype-phenotype correlation of CACNA1A variants in children with epilepsy.

AIM: To explore the genotypes and phenotypes of CACNA1A variants in children with epilepsy. METHOD: Eighteen children (six males, 12 females) with CACNA1A variants were identified using next-generation sequencing. RESULTS: There were 14 missense variants, two nonsense variants, one frameshift variant, and one splice site variant. Sixteen variants were de novo. Age at seizure onset ranged from 1 day to 8 years; median age was 8 months. Multiple seizure types were observed, including focal, generalized tonic-clonic, myoclonic, and absence seizures, as well as epileptic spasms and tonic seizures. Focal motor status epilepticus occurred in 10 individuals and generalized motor status epilepticus occurred in two individuals. All 18 children showed developmental delay. Focal motor status epilepticus resulted in cerebral atrophy in five individuals, mainly on the contralateral side. Interictal electroencephalogram showed focal discharges in 12 individuals, whereas five individuals had generalized discharges. Three individuals were seizure-free, whereas 15 still had seizures and five had recurrent status epilepticus at last follow-up. INTERPRETATION: Most children with epilepsy and CACNA1A variants had early seizure onset and developmental delay. Focal seizure was the most common seizure type. Most patients experienced status epilepticus. Unilateral cerebral atrophy could occur after focal motor status epilepticus. Patients with CACNA1A variants located in the transmembrane region may be at high risk of status epilepticus.

Phenotypes and genotypes of mitochondrial diseases with mtDNA variations in Chinese children: A multi-center study.

Mitochondrial DNA (mtDNA) associated mitochondrial diseases hold a crucial position but comprehensive and systematic studies are relatively rare. Among the 262 patients of four children's hospitals in China, 96%-point mutations (30 alleles in 11 genes encoding tRNA, rRNA, Complex I and V) and 4%-deletions (seven of ten had not been reported before) were identified as the cause of 14 phenotypes. MILS presented the highest genetic heterogeneity, while the m.3243A > G mutation was the only "hotspot" mutation with a wide range of phenotypes. The degrees of heteroplasmy in the leukocytes of MM were higher than MELAS. The heteroplasmy level of patients was higher than that in mild and carrier group, while we found low-level heteroplasmy pathogenic mutations as well. Some homoplasmic variations (e.g., m.9176 T > C mutation) are having high incomplete penetrance. For a suspected MELAS, m.3243A > G mutation was recommended to detect first; while for a suspected LS, trios-WES and mtDNA genome sequencing by NGS were recommended first in both blood and urine.