LncRNA SNHG1 alleviates OGD induced injury in BMEC via miR-338/HIF-1α axis.

BACKGROUND: Brain microvascular endothelial cell (BMEC) is an important therapeutic target for the inhibition of brain vascular dysfunction in ischemic stroke. Expression of long non-coding RNA SNHG1 is reportedly upregulated in BMEC after OGD. The present study aims to investigate the potential roles of SNHG1 in OGD-induced injury in BMEC. METHODS: Mice primary brain microvascular endothelial cells (BMEC) were cultured under "normal" or "oxygen/glucose-deprived" (OGD) conditions. The expression of SNHG1 and miR-338 after OGD were examined by qPCR. shRNA against SNHG1 was used to knockdown SNHG1 in BMEC. MiR-338-3p mimic and inhibitor were used to change the expression of miR-338 in BMEC. The relationship between SNHG1 and miR-338, and the relationship between miR-338 and HIF-1α were clarified using RNA pull-down and luciferase reporter gene assays, respectively. RESULTS: SNHG1 and miR-338 were upregulated in OGD induced BMEC. SNHG1 silence aggravated OGD-induced cell apoptosis by down-regulating Bcl-2, HIF-1α and VEGF-A, and upregulating caspase 3 activity and Bax. MiR-338 was upregulated in SNHG1-silenced BMEC. RNA pull-down assays showed that SNHG1 could be directly bound by miR-338. In addition, miR-338 overexpression reduced cell viability in OGD while miR-338 inhibition protected BMEC against OGD-induced injury. Furthermore, luciferase reporter assay showed that HIF-1α was a direct target of miR-338. CONCLUSIONS: SNHG1 exerted protective effects against OGD induced injury via sponging miR-338, thus upregulating HIF-1α/VEGF-A in BMEC.

Genetic Analysis of LRRK1 and LRRK2 Variants in Essential Tremor Patients.

AIMS: Essential tremor (ET) is one of the most common adult-onset movement disorders. ET and Parkinson's disease (PD) overlap clinically and pathologically, which prompted this investigation into the association of PD risk variants in ET patients. This study was designed to explore the role of variants of two PD-related genes LRRK1 and LRRK2 in a Han Chinese ET population. MATERIALS AND METHODS: Genetic analysis of LRRK1, rs2924835, and LRRK2, rs34594498, rs34410987, and rs33949390 variants was conducted on 200 Han Chinese patients with ET and 434 ethnically matched normal controls. RESULTS: No statistically significant differences were identified in either genotypic or allelic frequencies of variants between the ET patients and the control cohort (all p > 0.05). Haplotype analysis of three LRRK2 variants (rs34594498, rs34410987, and rs33949390) showed no haplotypes displayed an association with ET risk (all p > 0.05). CONCLUSIONS: The data suggest that LRRK1 variant (rs2924835) and LRRK2 variants (rs34594498, rs34410987, and rs33949390) are not associated with ET in this Han Chinese population.

Screening for SH3TC2, PMP2, and BSCL2 Variants in a Cohort of Chinese Patients with Charcot-Marie-Tooth.

BACKGROUND: SH3TC2, PMP2, and BSCL2 genes are related to autosomal recessive (AR) Charcot-Marie-Tooth (CMT) disease type 1, autosomal dominant (AD)-CMT1, and AD-CMT2, respectively. Pathogenic variants in these three genes were not well documented in Chinese CMT patients. Therefore, this study aims to detect SH3TC2, PMP2, and BSCL2 pathogenic variants in a cohort of 315 unrelated Chinese CMT families. METHODS: A total of 315 probands from 315 unrelated Chinese CMT families were recruited from the Department of Neurology of Third Xiangya Hospital and Xiangya Hospital. We screened for SH3TC2 pathogenic variants in 84 AR or sporadic CMT probands, PMP2 pathogenic variants in 39 AD or sporadic CMT1 probands, and BSCL2 pathogenic variants in 50 AD or sporadic CMT2 probands, using polymerase chain reaction and Sanger sequencing. All these patients were out of 315 unrelated Chinese CMT families and genetically undiagnosed after exclusion of pathogenic variants of PMP22, MFN2, MPZ, GJB1, GDAP1, HSPB1, HSPB8, EGR2, NEFL, and RAB7. Candidate variants were analyzed based on the standards and guidelines of American College of Medical Genetics and Genomics (ACMG). Clinical features were reevaluated. RESULTS: We identified three novel heterozygous variants such as p.L95V (c.283C>G), p.L1048P (c.3143T>C), and p.V1105M (c.3313G>A) of SH3TC2 gene and no pathogenic variants of PMP2 and BSCL2 genes. Although evaluation in silico and screening in the healthy control revealed that the three SH3TC2 variants were likely pathogenic, no second allele variants were discovered. According to the standards and guidelines of ACMG, the heterozygous SH3TC2 variants such as p.L95V, p.L1048P, and p.V1105M were considered to be of uncertain significance. CONCLUSIONS: SH3TC2, PMP2, and BSCL2 pathogenic variants might be rare in Chinese CMT patients. Further studies to confirm our findings are needed.

Krüppel-like factor 4 regulates amyloid-ß (Aß)-induced neuroinflammation in Alzheimer's disease.

Alzheimer's disease (AD), one of the most common neurodegenerative diseases, is characterized by extracellular deposition of amyloid-ß (Aß) peptide, and neuro-inflammatory processes mediated by microglial activation are known to play a pivotal role in AD. However, the expression pattern and function of Krüppel-like factor (KLF) 4 in AD remain unknown. In this study, KLF4 was found to be increased at both the gene and protein levels in response to incubation with oligomeric Aß42 in a dose-dependent manner in BV2 microglial cells. An in vivo study also displayed that expression of KLF4 in the brains of J20 transgenic AD model mice was increased due to accumulation of Aß. Mechanistically, activation of p53 resulting from an increase in phosphorylation at ser15 was verified as the mediator of the oligomeric Aß42-induced expression of KLF4. Subsequent experiments have demonstrated that KLF4 silencing in BV2 cells attenuates oligomeric Aß42-induced neuroinflammation by ameliorating the release of proinflammatory cytokines, such as tumor necrosis factor-a (TNF-α), interleukin (IL)-1ß, IL-6, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). In addition, overexpression of KLF4 promoted oligomeric Aß42-induced neuroinflammation by exacerbating the release of pro-inflammatory factors. These results suggest a KLF4 plays a potential role in oligomeric Aß42-induced neurotoxicity and the pathogenesis of AD.

Mutant presenilin2 promotes apoptosis through the p53/miR-34a axis in neuronal cells.

Neurodegenerative disorders have attracted attention in last decades due to their high incidence in the world. The p53/miR-34a axis triggers apoptosis and suppresses viability in multiple types of cells, but little is known about its role in neurodegenerative diseases. In this study, we showed that presenilin (PS)-2, a major gene associated with familial Alzheimer's disease (AD) could trigger the apoptosis through the p53/miR-34a axis in PC12 cells. First we found that PC12 cell viability was downregulated by PS-2 and mutant PS-2 overexpression, especially by mutant PS-2 overexpression. Then, we established a mutant PS-2-overexpressing PC12 cell line and confirmed that mutant PS-2 induced not only p53 but also miR-34a expression. The transfection of miR-34a inhibitor reversed PS-2-induced effects on cellular viability and apoptosis. Mutant PS-2 overexpression promoted caspase-3 expression, reduced Sirt1 and Bcl-2 expression, all of which were miR-34a downstream genes related with cell apoptosis. Moreover, mutant PS-2 also activated the p53/miR-34a axis and induced apoptosis in AD transgenic mice brain. These results implied that mutant PS-2 might promote the apoptosis of neuronal cells through triggering the p53/miR-34a axis. Altogether our results provide a novel insight into neurodegenerative disease and deepen our understandings of AD pathogenic processes.

IGHMBP2-related clinical and genetic features in a cohort of Chinese Charcot-Marie-Tooth disease type 2 patients.

IGHMBP2 mutations had been exclusively associated with spinal muscular atrophy with respiratory distress type I. However, increasing AR-CMT2S cases without respiratory failure caused by IGHMBP2 mutations have been reported in the past two years. We detected IGHMBP2 mutations in a cohort of Chinese CMT2 patients using genes panel testing, polymerase chain reaction and Sanger sequencing. We found four families with autosomal recessive IGHMBP2 mutations, and the frequency of IGHMBP2 mutations is 6.5% in CMT2 without dominant inheritance. We detected a homozygous variant c.1235 + 3A > G in Family 1, compound heterozygous variants c.1737C > A and c.2597_2598delAG in Family 2, compound heterozygous variants c.1489G > A and c.2356delG in Family 3, compound heterozygous variants c.1909C > T and c.1061-2A > G in Family 4. According to the standards and guidelines of the American College of Medical Genetics and Genomics, all the above variants were classified as pathogenic. Four mutations, c.1489G > A, c.2356delG, c.2597_2598delAG and c.1061-2A > G, are reported for the first time. The novel splice acceptor site mutation c.1061-2A > G resulted in deletion of 175 bp, and it was predicted to lead to a frameshift after codon 354 with a premature termination at codon 364. In conclusion, mutation screening of IGHMBP2 should be especially considered in AR-CMT2 and sporadic CMT2 patients.

MFN2-related genetic and clinical features in a cohort of Chinese CMT2 patients.

Charcot-Marie-Tooth disease 2A (CMT2A), caused by mutations in the mitofusin 2 gene (MFN2), is the most common CMT2 subtype. The aim of our study is to assess the frequency and summarize the genetic and clinical characteristics of Chinese CMT2A patients. A total of 17 coding exons of MFN2 were detected by direct sequencing in 82 unrelated Chinese families diagnosed as CMT2. Clinical evaluations were analyzed among CMT2A patients. We identified 14 missense variants in 9 sporadic and 6 familial cases, including four novel mutations (T129A, S249F, Q367P, and Q674L), 4 known mutations (R94W, R94Q, T105M, C132Y, M376V and Q751X), and 4 rare missense variants (K120E, C217F, K307E and T356S). A total of 23 patients had early-onset phenotype. Two patients had a CMTNS score of 0 to 10; 16 had a score of 11 to 20; and 7 had a score greater than 20. Five patients were confirmed a de novo origin. Six of 14 variants were located or closed to the GTPase domain. We report four novel mutations and four rare missense variants. MFN2 mutations account for 18% of CMT2 families in mainland China. The common characteristics of Chinese pedigree are early disease onset and moderate phenotypes.

A SIGMAR1 splice-site mutation causes distal hereditary motor neuropathy.

OBJECTIVE: To identify the underlying genetic cause in a consanguineous Chinese family segregating distal hereditary motor neuropathy (dHMN) in an autosomal recessive pattern. METHODS: We used whole-exome sequencing and homozygosity mapping to detect the genetic variant in 2 affected individuals of the consanguineous Chinese family with dHMN. RNA analysis of peripheral blood leukocytes and immunofluorescence and immunoblotting of stable cell lines were performed to support the pathogenicity of the identified mutation. RESULTS: We identified 3 shared novel homozygous variants in 3 shared homozygous regions of the affected individuals. Sequencing of these 3 variants in family members revealed the c.151+1G>T mutation in SIGMAR1 gene, which located in homozygous region spanning approximately 5.3 Mb at chromosome 9p13.1-p13.3, segregated with the dHMN phenotype. The mutation causes an alternative splicing event and generates a transcript variant with an in-frame deletion of 60 base pairs in exon 1 (c.92_151del), and results in an internally shortened protein σ1R(31_50del). The proteasomal inhibitor treatment increased the intracellular amount of σ1R(31_50del) and led to the formation of nuclear aggregates. Stable expressing σ1R(31_50del) induced endoplasmic reticulum stress and enhanced apoptosis. CONCLUSION: The homozygous c.151+1G>T mutation in SIGMAR1 caused a novel form of autosomal recessive dHMN in a Chinese consanguineous family. Endoplasmic reticulum stress may have a role in the pathogenesis of dHMN.

Epigenetic modulation of Cdk5 contributes to memory deficiency induced by amyloid fibrils.

Alzheimer's disease (AD) is a frequent neurodegenerative disorder with progressive neuroinflammation, loss of synaptic plasticity in central neurons and memory deficiency. Numerous studies demonstrated the epigenetic modification of the expression of specific genes involved in the pathogenesis of amyloid-associated memory deficiency. It was also reported that dysregulation of cyclin-dependent kinase 5 (Cdk5) activity critically contributed to the synaptic dysfunction and memory deficiency in the rodent model of AD. The present study aims to study the epigenetic mechanism underlying the altered Cdk5 activity and its functional significance in the rats with hippocampal infusion of amyloid fibrils. Significantly increased mRNA and expression of Cdk5 were observed in the hippocampal CA1 in the rats injected with amyloid fibrils. Increased acetylation of histone H3 was detected in the Cdk5 promoter region in hippocampal CA1 in these rats. Further chromatin immunoprecipitation and bisulfite sequencing studies illustrated the decreased cytosine methylation in the Cdk5 promoter region in hippocampal CA1 in the modeled rats. Administration with Cdk5 inhibitor roscovitine significantly attenuated the phosphorylation of tau, recovered the synaptic dysfunction of hippocampal CA1 neurons, and improved the behavioral performance in the Morris water maze test and novel object recognition test in the rats injected with amyloid fibrils. These results elucidate the potential epigenetic mechanism underlying the upregulated expression of Cdk5 induced by amyloid fibrils and provided novel insights into the pathogenic mechanism of Alzheimer's disease.

Bag5 protects neuronal cells from amyloid ß-induced cell death.

The pathological mechanism of Alzheimer's disease (AD) needs to be elucidated. The Bcl-2 associated athanogene 5 (Bag5) is an important member in the Bag family. However, the role of Bag5 in AD has not yet been elucidated. In this study, we found that expression of Bag5 is elevated in the brains of AD transgenic Tg2576 mice at both mRNA levels and proteins. In vitro experiments indicated that Aß1-42 treatment led to the upregulation of Bag5 in a dose-dependent manner. In addition, our results indicated that inhibition of Bag5 using small RNA interferences exacerbated Aß1-42-induced neurotoxicity. On one hand, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assay demonstrated that inhibition of Bag5 exacerbated Aß1-42-related cell death. On the other hand, silence of endogenous Bag5 promotes the generation of reactive oxygen species (ROS) and malondialdehyde (MDA) induced by Aß1-42. Finally and importantly, it was shown that knockdown of Bag5 exacerbated Aß1-42-induced apoptosis and caspase-3 cleavage. These data suggest that induction of Bag5 might have a neuroprotective effect in AD.

PMP22-Related neuropathies and other clinical manifestations in Chinese han patients with charcot-marie-tooth disease type 1.

INTRODUCTION: Most cases of Charcot-Marie-Tooth (CMT) disease are caused by mutations in the peripheral myelin protein 22 gene (PMP22), including heterozygous duplications (CMT1A), deletions (HNPP), and point mutations (CMT1E). METHODS: Single-nucleotide polymorphism (SNP) arrays were used to study PMP22 mutations based on the results of multiplex ligation-dependent probe amplification (MLPA) and polymerase chain reaction-restriction fragment length polymorphism methods in 77 Chinese Han families with CMT1. PMP22 sequencing was performed in MLPA-negative probands. Clinical characteristics were collected for all CMT1A/HNPP probands and their family members. RESULTS: Twenty-one of 77 CMT1 probands (27.3%) carried duplication/deletion (dup/del) copynumber variants. No point mutations were detected. SNP array and MLPA seem to have similar sensitivity. Fifty-seven patients from 19 CMT1A families had the classical CMT phenotype, except for 1 with concomitant CIDP. Two HNPP probands presented with acute ulnar nerve palsy or recurrent sural nerve palsy, respectively. CONCLUSIONS: The SNP array has wide coverage, high sensitivity, and high resolution and can be used as a screening tool to detect PMP22 dup/del as shown in this Chinese Han population.

A novel transgenic mouse model of Chinese Charcot-Marie-Tooth disease type 2L.

We previously found that the K141N mutation in heat shock protein B8 (HSPB8) was responsible for Charcot-Marie-Tooth disease type 2L in a large Chinese family. The objective of the present study was to generate a transgenic mouse model bearing the K141N mutation in the human HSPB8 gene, and to determine whether this (K141N)HSPB8 transgenic mouse model would manifest the clinical phenotype of Charcot-Marie-Tooth disease type 2L, and consequently be suitable for use in studies of disease pathogenesis. Transgenic mice overexpressing (K141N)HSPB8 were generated using K141N mutant HSPB8 cDNA cloned into a pCAGGS plasmid driven by a human cytomegalovirus expression system. PCR and western blot analysis confirmed integration of the (K141N)HSPB8 gene and widespread expression in tissues of the transgenic mice. The (K141N)HSPB8 transgenic mice exhibited decreased muscle strength in the hind limbs and impaired motor coordination, but no obvious sensory disturbance at 6 months of age by behavioral assessment. Electrophysiological analysis showed that the compound motor action potential amplitude in the sciatic nerve was significantly decreased, but motor nerve conduction velocity remained normal at 6 months of age. Pathological analysis of the sciatic nerve showed reduced myelinated fiber density, notable axonal edema and vacuolar degeneration in (K141N)HSPB8 transgenic mice, suggesting axonal involvement in the peripheral nerve damage in these animals. These findings indicate that the (K141N)HSPB8 transgenic mouse successfully models Charcot-Marie-Tooth disease type 2L and can be used to study the pathogenesis of the disease.

Two novel MPZ mutations in Chinese CMT patients.

To investigate the myelin protein zero (MPZ) gene mutation and related clinical features in Chinese Charcot-Marie-Tooth (CMT) patients, we screened the coding sequence of MPZ in 70 unrelated CMT index patients after excluding the PMP22 duplication, Cx32 and MFN2 mutations. We found four different missense mutations: c.194C>T, c.242A>T, c.371C>T, and c.419C>G. The frequency of MPZ mutation was approximately 4.35% of the total, 3.08% of CMT1, and 6% of CMT2. Mutations c.242A>T and c.419C>G are novel. The mutation c.242A>T exhibited late onset and rapidly progressive CMT2 phenotype. The mutation c.419C>G exhibited relatively late onset and slowly progressive CMT1 phenotype.

Acute myelitis in a patient with vogt-koyanagi-harada disease: case report and review of the literature.

BACKGROUND: Vogt-Koyanagi-Harada (VKH) disease is characterized by bilateral granulomatous uveitis with neurologic, auditory, and dermatologic manifestations. However, acute myelitis complicating VKH disease has rarely been reported. CASE REPORT: A 50-year-old Chinese Han woman presented with difficulty walking, numbness on the left side of the body, and difficulty with urination. The patient was diagnosed with incomplete VKH disease and received corticosteroid treatment prior to the neurological presentation. Acute myelitis was diagnosed based on both clinical and spinal-cord MRI findings. CONCLUSIONS: Clinicians should consider acute myelitis as a rare possible neurological manifestation in VKH disease patients, and early systemic administration of corticosteroids will suppress the acute inflammatory process and prevent recurrences. This report raises the possibility that VKH disease and acute myelitis share common pathogenic pathways.

[Analysis of CX32 gene mutation and related clinical features in Chinese Han Charcot-Marie-Tooth families].

OBJECTIVE: To analyze the mutation of CX32 gene and related clinical features in Chinese Han patients with Charcot-Marie-Tooth (CMT) disease. METHODS: Thirty-four CMT families, from 2004 to 2011 at Departments of Neurology, Xiangya Hospital, Third Xiangya Hospital and National Key Laboratory of Medical Genetics, were selected for CX32 mutation screening after the exclusion of the PMP22 duplication and male-to-male transmission. Mutation analysis was carried out by polymerase chain reaction (PCR) plus direct sequencing. Analyses of clinical, electrophysiological and pathological features in 11 patients from 6 CMTX1 families were performed by 2 neurologists. RESULTS: Five CX32 gene mutations were detected in 6 CMT families: c.37G > A, c.65G > A, c.246C > G, c.256A > G and c.533A > G. Among them, c.246C > G and c.533A > G were firstly reported. The clinical manifestations included progressive distal muscle atrophy and weakness, areflexia, sensory abnormalities and pes vacus. Nerve conduction velocity ranged from 21.7 to 49.3 m/s. Both demyelination and axonal degeneration were detected in nerve biopsy. CONCLUSIONS: CMT1X has a frequency of around 9% in our study. The male patients tend to have more serious clinical features and their electrophysiological and pathological changes are intermediate. CX32 mutation analysis helps to confirm the genetic diagnosis of CMT so as to provide genetic counseling and reproductive guidance and elucidate its pathogenesis.

Rapid genetic screening of Charcot-Marie-Tooth disease type 1A and hereditary neuropathy with liability to pressure palsies patients.

We used the allele-specific PCR-double digestion method on peripheral myelin protein 22 (PMP22) to determine duplication and deletion mutations in the proband and family members of one family with Charcot-Marie-Tooth disease type 1 and one family with hereditary neuropathy with liability to pressure palsies. The proband and one subclinical family member from the Charcot-Marie-Tooth disease type 1 family had a PMP22 gene duplication; one patient from the hereditary neuropathy with liability to pressure palsies family had a PMP22 gene deletion. Electron microscopic analysis of ultrathin sections of the superficial peroneal nerve from the two probands demonstrated demyelination and myelin sheath hyperplasia, as well as an 'onion-like' structure in the Charcot-Marie-Tooth disease type 1A patient. We observed an irregular thickened myelin sheath and 'mouse-nibbled'-like changes in the patient with hereditary neuropathy with liability to pressure palsies. In the Charcot-Marie-Tooth disease type 1A patient, nerve electrophysiological examination revealed moderate-to-severe reductions in the motor and sensory conduction velocities of the bilateral median nerve, ulnar nerve, tibial nerve, and sural nerve. Moreover, the compound muscle action potential amplitude was decreased. In the patient with hereditary neuropathy with liability to pressure palsies, the nerve conduction velocity of the bilateral tibial nerve and sural nerve was moderately reduced, and the nerve conduction velocity of the median nerve and ulnar nerve of both upper extremities was slightly reduced.

[Cellular expression of (R127W)HSPB1 and its co-localization with neurofilament light chain].

OBJECTIVE: To observe the cellular expression of (R127W) HSPB1 and its influence on neurofilament light chain (NFL) self-assembly and co-localization with NFL. METHODS: Eukaryotic expression vectors pEGFPN1-(wt) HSPB1 and pEGFPN1- (R127W) HSPB1 were constructed. Hela cells were transiently transfected with pEGFPN1-(wt) HSPB1 or pEGFPN1- (R127W) HSPB1 and observed under a confocal microscope. Hela cells were also transiently co-transfected with Pcl-NFL and pEGFPN1-(wt)HSPB1, or pCL-NFL and pEGFPN1-(R127W)HSPB1. The self-assembly of NFL was observed and the co-localization study of HSPB1/ (R127W)HSPB1 with NFL was carried out in these two cell models by immunofluorescence technique. RESULTS: The aggregates formed by EGFP-(R127W)HSPB1 predominantly located around the nucleus, and EGFP-(wt)HSPB1 showed diffusion pattern in Hela cells. When co expressed with EGFP-(wt)HSPB1, NFL formed homogeneous structure in cytosol. When co-expressed with EGFP-(R127W)HSPB1, however, NFL had amorphous staining pattern predominantly consisting of NFL aggregates, and NFL co-localized with (R127W)HSPB1 in these aggregates. CONCLUSION: The R127W mutant of HSPB1 may have reduced capacity to serve as a chaperone to prevent aggregate formation, and fail to correctly organize the neurofilament network. Dysfunction of the axon cytoskeleton and axon transport may be the primary mechanism of R127W mutation of HSPB1 in the pathogenesis of Charcot-Marie-Tooth disease.

[Mutation analysis of LITAF, RAB7, LMNA and MTMR2 genes in Chinese Charcot-Marie-Tooth disease.].

The purpose of this study was to understand the mutation features of lipopolysaccharide-induced tumor necrosis factor-alpha factor (LITAF), ras-associated protein RAB7 (RAB7), lamin A/C (LMNA) and myotubularin-related protein 2 (MTMR2) genes in Chinese Charcot-Marie-Tooth disease (CMT) patients. Mutation analysis of LITAF gene was carried out using PCR combined with DNA sequencing, and mutation analysis of RAB7 gene by PCR-single strand conformation polymorphism (PCR-SSCP) combined with DNA sequencing in 33 CMT patients including 6 probands of autosomal domi-nated CMT families and 27 sporadic patients; mutation analysis of LMNA and MTMR2 genes was observed using PCR-SSCP combined with DNA sequencing in 41 CMT patients, including 14 probands of autosomal recessive CMT fami-lies and 27 sporadic patients. Two sequence variations c.269G-->A and c.274A-->G were detected in LITAF gene and two sequence variations c.1243G-->A and c.1910C-->T were detected in LMNA gene. No sequence variation was found in RAB7 and MTMR2 gene. Variations of c.269G-->A in LITAF gene and c.1243G-->A, c.1910C-->T in LMNA gene are newly found SNPs in this study. Variation of c.274A-->G in LITAF gene is known SNP reported in SNP database. Mutations in LITAF, RAB7, LMNA, and MTMR2 genes are rare in Chinese CMT patients.

Mutation detection in candidate genes for benign familial infantile seizures on a novel locus.

Benign familial infantile seizures (BFIS) is an autosomal dominant epileptic syndrome characterized by afebrile partial seizures with or without secondary generalized tonic-clonic seizures beginning at three to ten months of age. Genetic studies have revealed three susceptibility chromosomal loci on 19q12-q13.1, 16p12-q12 and 2q24. Previously we described the novel locus on 1p36.12-p35.1 for a Chinese family affected with BFIS, and below is a subsequent mutation analysis of candidate genes for the mapped chromosome region. Forty-five genes were selected and subjected to mutation analysis. Thirty-six nucleotide variants were found, none of which led to pathogenic changes, thereby were identified as nucleotide polymorphisms. The analyses suggest those candidate genes that were detected might not be involved in the epileptogenesis of pure BFIS, at least in the Chinese family we studied.