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Aims CHD4 gene, encoding chromodomain helicase DNA‐binding protein 4, is a vital gene for fetal development. In this study, we aimed to explore the association between CHD4 variants and idiopathic epilepsy. Methods Trios‐based whole‐exome sequencing was performed in a cohort of 482 patients with childhood idiopathic epilepsy. The Clinical Validity Framework of ClinGen and an evaluating method from five clinical‐genetic aspects were used to determine the association between CHD4 variants and epilepsy. Results Four novel heterozygous missense mutations in CHD4, including two de novo mutations (c.1597A>G/p.K533E and c.4936G>A/p.E1646K) and two inherited mutations with co‐segregation (c.856C>G/p.P286A and c.4977C>G/p.D1659E), were identified in four unrelated families with eight individuals affected. Seven affected individuals had sinus arrhythmia. From the molecular sub‐regional point of view, the missense mutations located in the central regions from SNF2‐like region to DUF1087 domain were associated with multisystem developmental disorders, while idiopathic epilepsy‐related mutations were outside this region. Strong evidence from ClinGen Clinical Validity Framework and evidences from four of the five clinical‐genetic aspects suggested an association between CHD4 variants and epilepsy. Conclusions CHD4 was potentially a candidate pathogenic gene of childhood idiopathic epilepsy with arrhythmia. The molecular sub‐regional effect of CHD4 mutations helped explaining the mechanisms underlying phenotypic variations., CHD4 missense mutations associated with multisystem developmental abnormalities were clustered in the central region from SNF2‐like region to DUF 1087 domain, while the variants associated with other mild phenotypes were located outside this region. The potentially molecular sub‐regional effects of missense mutations may explain for the phenotypic severity of CHD4 mutations and would help understand the underlying mechanisms of phenotypic variation.

Objectives To describe the clinical and genetic features of a Chinese peroxisome biogenesis disorder 6B patient with PEX10 mutations and review PEX10–related peroxisomal disorders. Patients and methods The proband is a 7-year-old boy with mild mental retardation and gait instability, intention tremor and nystagmus. An extensive clinical and laboratory evaluation including molecular genetic studies was performed. Genomic DNA was extracted from peripheral blood using the standardized phenol/chloroform extraction method, and the coding region of the PEX10 gene was sequenced in three family members. Results Cerebral MRI showed cerebellar atrophy. Magnetic resonance spectroscopy revealed a decreased N-acetyl aspartate peak in the cerebellum. Nerve conduction velocity examination found prolonged motor and sensory nerve potential latencies (proximal obvious), decreased potential amplitude, and slow nerve conduction velocity. Routine blood tests and biochemistries were abnormal. The PEX10 gene test showed compound heterozygous mutations (c.209 G > A, p. G70E and c.830 T > C, p. L277 P). The mutation c.830 T > C, p. L277 P has been previously reported, whereas c.209 G > A, p. G70E is novel. Conclusion We identified an ataxia case of peroxisome biogenesis disorder 6B caused by novel compound heterozygous mutations of the PEX10 gene. Peroxisome biogenesis disorders should be considered in the differential diagnosis of autosomal recessive ataxia, especially cases with early onset.

OBJECTIVE: To evaluate the efficacy and safety of cyclophosphamide as a second-line drug in the treatment of children with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. METHODS: Six children with anti-NMDAR encephalitis, who showed poor response to steroids and intravenous immunoglobulin, were given cyclophosphamide as a second-line immunotherapy. Follow-up was performed to evaluate the efficacy and safety of cyclophosphamide. RESULTS: After first-line immunotherapy for 1-4 weeks, the six patients had reduced psychiatric symptoms, seizures, and involuntary movements; three patients had an improved level of consciousness and were able to make simple conversations. However, all the patients still showed slow response, as well as cortical dysfunction symptoms such as aphasia, alexia, agraphia, acalculia, apraxia, and movement disorders. The six patients continued to receive cyclophosphamide as a sequential therapy. They were able to answer simple questions 7 days after treatment. Three school-aged patients were able to make simple calculation, had greatly improved reading and writing ability, and almost recovered self-care ability 2-3 weeks later. The cognitive function of the six patients was almost restored to the level before the onset of disease, and their living ability returned to normal 2-3 months later. During the treatment period, there were no adverse reactions or abnormal results of routine blood test and liver and kidney function tests. CONCLUSIONS: Children with anti-NMDAR encephalitis should be given appropriate immunotherapy as soon as possible. Cyclophosphamide as a sequential therapy has good efficacy and safety.

To determine the frequency of different subtypes of spinocerebellar ataxias (SCAs) in the Han nationality of Hunan province in China.The mutations of SCA1, SCA2, SCA3, SCA6, SCA7, SCA17, and dentatorulral-pallidoluysian (DRPLA) were detected with the polymerase chain reaction (PCR), denaturing polyacrylamide gel and DNA sequencing techniques in 139 autosomal dominant SCA families and 61 sporadic SCA patients.Of the 139 families, 11 (7.9%) were positive for SCA1, 9(6.5%) were positive for SCA2, 71 (51.1%) were positive for SCA3, 4 (2.9%) were positive for SCA6, 2 (1.4%) were positive for SCA7, and none was positive for SCA17 and DRPLA. There was 1 SCA2 patient, 3 SCA3 patients, 1 SCA6 patient in the 61 sporadic SCA patients.The frequency of SCA3 is substantially higher than that of SCA1 and SCA2 in the autosomal dominant SCA patients in the Han nationality of Hunan province. SCA6 and SCA7 are rare subtypes.

To study the clinical characteristics and molecular biology of hereditary spinocerebellar ataxia type 7 (SCA7).Peripheral blood samples were collected from 245 with autosomal dominant SCA from 184 families and 71 sporadic SCA patients. Polymerase chain reaction, polyacrylamide gel electrophoresis, and capillary electrophoresis technique were used to detect the SCA7 (CAG) n trinucleotide repeat mutations. 163 healthy persons were used as controls. The abnormal allele fragments were sequenced by ABI 377 DNA sequencing machine.Three SCA families with 15 patients were identified with a positive rate of 1.6%. DNA sequencing showed that the abnormal SCA7 alleles with CAG repeat were expanded to 38 to 71 repeats, and the normal SCA7 alleles were carried from 6 to 15 CAG repeats. Analysis of parent-child couples demonstrated the existence of marked anticipation in 2 families, especially in paternal transmission. Linkage analysis found a maximum two-point LOD score of 2.82 in the microsatellite D3S1300 at recombination fraction (theta = 0.00).CAG expansion is the pathogenic cause of SCA7, a rare subtype of SCA. The 38 CAG is the minimum pathological expansion in mainland China.