OBJECTIVE: To explore the clinical characteristics and genetic etiology of a child with multiple pterygium syndrome (MPS). METHODS: A child with MPS who was treated at the Orthopedics Department of Guangzhou Women and Children's Medical Center Affiliated to Guangzhou Medical University on August 19, 2020 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and her parents were also collected. Whole exome sequencing (WES) was carried out for the child. Candidate variant was validated by Sanger sequencing of her parents and bioinformatic analysis. RESULTS: The child, an 11-year-old female, had a complain of "scoliosis found 8 years before and aggravated with unequal shoulder height for 1 year". WES results revealed that she has carried a homozygous c.55+1G>C splice variant of the CHRNG gene, for which both of her parents were heterozygous carriers. By bioinformatic analysis, the c.55+1G>C variant has not been recorded by the CNKI, Wanfang data knowledge service platform and HGMG databases. Analysis with Multain online software suggested that the amino acid encoded by this site is highly conserved among various species. As predicted with the CRYP-SKIP online software, the probability of activation and skipping of the potential splice site in exon 1 caused by this variant is 0.30 and 0.70, respectively. The child was diagnosed with MPS. CONCLUSION The CHRNG gene c.55+1G>C variant probably underlay the MPS in this patient.
Humans ; Child ; Female ; Abnormalities, Multiple/genetics* ; Malignant Hyperthermia/genetics* ; Skin Abnormalities/genetics* ; Heterozygote ; Mutation ; Receptors, Nicotinic/genetics*

OBJECTIVETo investigate the association between neuronal nicotinic acetylcholine receptor alpha 7 subunit (CHRNA7) gene and schizophrenia.

METHODSThe three polymorphisms rs2337980, rs1909884, rs883473 in CHRNA7 gene were detected based on PCR and polyacrylamide gel microarray in 129 schizophrenic trios. The results of genotyping were analyzed by haplotype relative risk analysis based on haplotype(HHRR), transmission disequilibrium test(TDT) and hyplotype analysis.

RESULTS(1)The HHRR analysis suggested that there was significant differences in rs2337980 allele frequencies between schizophrenia group and dummy control group(P= 0.017); (2)In TDT test, there may be transmission disequilibrium between rs2337980 and schizophrenia, the heterozygous parents excessively transferred the C allele to patients (P= 0.021); (3)The haplotype between rs2337980 and rs1909884 as well as the hyplotype among rs2337980, rs1909884 and rs883473 may have significant association with schizophrenia (global P= 0.034; global P= 0.027), the T-C and T-C-T hyplotype may have transmission disequilibrium with schizophrenia.

CONCLUSIONThere may be association between CHRNA7 gene polymorphisms and schizophrenia, the variant allele T in rs2337980 may have a protective effect to schizophrenia.

Adolescent ; Adult ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; genetics ; Haplotypes ; Humans ; Linkage Disequilibrium ; genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; genetics ; Receptors, Nicotinic ; genetics ; Schizophrenia ; genetics ; Young Adult ; alpha7 Nicotinic Acetylcholine Receptor

OBJECTIVETo detect over-expression of AChR-gamma mRNA in rhabdomyosarcoma tissues by duplex RT-PCR and discuss its potential in diagnosis of rhabdomyosarcoma.

METHODSDuplex RT-PCR was applied to the simultaneous detection of AChR-alpha and gamma subunit messenger RNA in 17 cases of rhabdomyosarcoma (9 ERMS, 6 ARMS, 2 PRMS). 20 cases of non-rhabdomyosarcomous small round cell tumors (6 poorly differentiated synovial sarcomas, 6 ES/PNET, 6 lymphomas, 2 neuroblastomas) and three normal muscle samples were also detected for AChR-alpha and gamma mRNA by the same method.

RESULTSAChR-alpha and AChR-gamma mRNA were expressed in all the cases of rhabdomyosarcoma. The rate of quantity in both transcripts was AChR-gamma/AChR-alpha >or= 1, but the rate for three normal muscle samples was < 1. Cases of non-rhabdomyosarcomous small round cell tumors were all negative for AChR-gamma.

CONCLUSIONAChR-gamma mRNA expression detected by molecular genetic methods is useful in diagnosis and differential diagnosis of rhabdomyosarcoma.

Diagnosis, Differential ; Humans ; Protein Subunits ; RNA, Messenger ; analysis ; Receptors, Cholinergic ; genetics ; Receptors, Nicotinic ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Rhabdomyosarcoma ; diagnosis

BACKGROUNDIt has been reported that the nicotinic acetylcholine receptor subunit α4 gene (CHRNA4) might be associated with smoking behaviors in the previous studies. Up to now, there are few reports on the relationship between CHRNA4 and smoking initiation. In this study, we tried to explore the role of two polymorphisms in CHRNA4 (rs1044396 and rs1044397) in smoking initiation and nicotine dependence in Chinese male smokers.

METHODSNine hundred and sixty-six Chinese male lifetime nonsmokers and smokers were assessed by the Fagerström test for nicotine dependence (FTND), smoking quantity (SQ) and the heaviness of smoking index (HSI). All subjects were divided into four groups based on their tobacco use history and the FTND scores. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to find two polymorphisms of CHRNA4 in these subjects.

RESULTSThe χ(2) test showed that rs1044396 was significantly associated with smoking initiation (χ(2) = 4.65, P = 0.031), while both rs1044396 and rs1044397 were significantly associated with nicotine dependence (χ(2) = 5.42, P = 0.020; χ(2) = 7.58, P = 0.005). Furthermore, the T-G (3.9%) haplotype of rs1044396-rs1044397 showed significant association with smoking initiation (χ(2) = 6.30, P = 0.012) and the C-G haplotype (58.9%) remained positive association with nicotine dependence (χ(2) = 8.64, P = 0.003) after Bonferroni correction. The C-G haplotype also significantly increased the HSI (P = 0.002) and FTND scores (P = 0.001) after Bonferroni correction.

CONCLUSIONThese findings suggest that CHRNA4 may be associated with smoking initiation and the C-G haplotype of rs1044396-rs1044397 might increase the vulnerability to nicotine dependence in Chinese male smokers.

Adult ; Aged ; Asian Continental Ancestry Group ; genetics ; Genetic Predisposition to Disease ; genetics ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; genetics ; Receptors, Nicotinic ; genetics ; Smoking ; adverse effects

OBJECTIVETo screen for polymorphisms in alpha 4 subunit (principal subunit of nAChR) gene (CHRNA4).

METHODSDNA was extracted from leukocytes of all subjects including 100 healthy senior people and 100 patients with Parkinson's disease (PD). The exons and adjacent intron regions of CHRNA4 were amplified with PCR. SNPs were screened by denatured high performance liquid chromatography (DHPLC) techniques and restriction fragment length polymorphisms. Potential mutations were confirmed by sequencing.

RESULTSTotal 10 polymorphisms were detected and identified in coding and adjacent intron regions of nAChR alpha 4 gene, that are 420C/T (0.873/0.127), 870C/T (0.828/0.172), 1440A/C (0.858/0.142), 1860C/T (0.738/0.262), 1890C/T (0.605/0.395), intron 5 +14T/C (0.553/0.447), intron 2 +22G/A (0.873/0.127), intron 3 +182 Del22bp (0.813/0.187), 1758C/T and 1809C/T (reference for coding sequence is GenBank SNPs 000744), of which the last three are novel mutations. PD patients appeared higher frequency of deletion in intron 3+182(0.235) than normal controls (0.140)(P=0.015).

CONCLUSIONnAChR alpha 4 gene is polymorphic. PD patients take higher frequency of intron3+182 Del 22 bp.

Aged ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Female ; Humans ; Male ; Molecular Sequence Data ; Parkinson Disease ; genetics ; Polymorphism, Genetic ; Receptors, Nicotinic ; genetics ; Sequence Analysis, DNA

OBJECTIVETo investigate the gene mutations of CHRNB2 and CHRNA2 in Chinese population with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE).

METHODSOne hundred and six Han nationality patients (74 sporadic and 32 familial) were recruited and studied. Mutational screening was performed by sequencing all the 6 coding exons of the CHRNB2 gene and exons 6 and 7 of the CHRNA2 gene including the donor and acceptor splice sites.

RESULTSThe results excluded the involvement of all known published mutations of the CHRNB2 and CHRNA2 genes. However, a novel synonymous mutation c.483C>T (H161H) and a single nucleotide polymorphism (c.1407C>G) of CHRNB2 gene were detected in two ADNFLE sporadic patients respectively. The nucleotide variation H161H was heterozygous and absent in 200 healthy control samples. The mutation was also found in the proband's unaffected mother.

CONCLUSIONOur study suggests that the mutations of CHRNB2 and CHRNA2 genes may be rare in Chinese ADNFLE population. The novel synonymous mutation of H161H has not been reported previously and its impact on the pathogenesis of ADNFLE needs to be further studied.

Asian Continental Ancestry Group ; genetics ; Child ; Child, Preschool ; DNA Mutational Analysis ; Epilepsy, Frontal Lobe ; genetics ; Female ; Genes, Dominant ; Humans ; Male ; Mutation ; Receptors, Nicotinic ; genetics

BACKGROUNDCongenital myasthenic syndromes are a group of rare disorders that are clinically and genetically heterogeneous and caused by mutations in the genes encoding proteins of the neuromuscular junction. Here, we described a Chinese family that presented with phenotypes of classic slow-channel congenital myasthenic syndrome (SCCMS).

METHODSClinical characteristics and electrophysiological features of three patients from a Chinese family were examined, and next-generation sequencing followed by direct sequencing was carried out.

RESULTSThe patients revealed variability in clinical and electrophysiological features. However, weakness, scoliosis, and repetitive-compound muscle action potential were found in all affected members in the family. A heterozygous C>T missense mutation at nucleotide 865 in acetylcholine receptor epsilon-subunit (CHRNE) gene that causes a leucine-to-phenylalanine substitution at position 289 (L289F) was found.

CONCLUSIONSWe reported a SCCMS family of Chinese origin. In the family, classical clinical phenotype with phenotypic variability among different members was found. Genetic testing could help diagnose this rare disease.

Adult ; DNA Mutational Analysis ; Electrophysiology ; Female ; Humans ; Male ; Mutation, Missense ; genetics ; Myasthenic Syndromes, Congenital ; genetics ; physiopathology ; Receptors, Nicotinic ; genetics ; Young Adult

OBJECTIVETo investigate the relevance between single nucleotide polymorphisms (SNPs) in CHRNA3-CHRNB4-CHRNA5 gene cluster and DNA damage levels in the coke oven workers.

METHODSA total of 309 male subjects from a steel plant in Northern China were divided into high exposure group (154 workers) and low exposure group (155 workers) according to the concentrations of plasma benzoapyrene-r-7, t-8, t-9, c-10-tetrahydrotetrol-albumin (BPDE-Alb) adducts. DNA damage levels of peripheral blood lymphocytes were examined by comet assay. Allelic discrimination of SNPs in CHRNA3-CHRNB4-CHRNA5 gene cluster were detected using Matrix-assisted laser desorption/ionization mass spectrometry.

RESULTSThe Olive tail moment (OTM) (1.23 ± 1.05) of peripheral blood lymphocytes in the high exposure group was significantly higher than that (0.80 ± 1.07) in the low exposure group (P < 0.01). In the high exposure group, OTM (1.64 ± 0.17) of subjects with rs667282CC genotype was significantly higher than those (0.95 ± 0.13 or 1.09 ± 0.11) of subjects with rs667282CT genotype or rs667282TT + CT genotype (P < 0.01); OTM (1.60 ± 0.17) of subjects with GG genotype at rs12910984 site was significantly higher than those (0.92 ± 0.13 or 1.07 ± 0.10) of subjects with AG genotype or AG + AA genotype (P < 0.01); OTM (1.35 ± 0.17 or 1.64 ± 0.17) of the TA/TA or CG/CG diplotype carriers was significantly higher than that (0.89 ± 0.13) of TA/CG diplotype carriers (P < 0.05). However, the relevance between genotypes of these SNPs and the DNA damage levels was not found in the low exposure group.

CONCLUSIONThe rs667282CC genotype and rs12910984GG genotype on CHRNA3-CHRNB4-CHRNA5 gene cluster are associated with increased DNA damage levels in the high PAHs exposure group.

Adult ; China ; Coke ; DNA Damage ; Genotype ; Humans ; Male ; Multigene Family ; Nerve Tissue Proteins ; genetics ; Occupational Exposure ; Polymorphism, Single Nucleotide ; Receptors, Nicotinic ; genetics

OBJECTIVETo investigate the influence of fluorosis on nicotinic acetylcholine receptors (nAChRs) in protein and gene levels in SH-SY5Y cells and the mechanism of the receptor modification.

METHODSSH-SY5Y cells, a human neuroblastoma cell line, were incubated with different concentrations of fluoride or with antioxidant for 48 hours. The functions of cells were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) method, and protein oxidation detected by carbonyl content; the alpha3 and alpha7 nAChR subunits in protein level were measured by Western blotting and in mRNA level by RT-polymerase chain reaction (RT-PCR).

RESULTSIn high-dose group as compared to the control, the decreased MTT (49%), increased protein oxidation (72%), and lower expression of alpha3 (51%) and alpha7 (47%) nAChR subunit proteins were obviously observed in SH-SY5Y cells. There were no changes in expression of nAChR subunit mRNAs between the cells treated with fluoride and those un-treated in controls. Prior treatment with antioxidant resulted in preventing the decrease of nAChR protein in cells exposed to the high doses of fluoride.

CONCLUSIONFluorosis should result in damage of cells and the declined expression of nAChRs in protein levels, but no influences on gene expression of the receptors in human neuroblastoma neurons. The decreased nAChR proteins might be involved in the mechanism of oxidative stress induced by fluorosis.

Cell Line, Tumor ; Fluoride Poisoning ; metabolism ; Fluorides ; toxicity ; Humans ; Neuroblastoma ; metabolism ; pathology ; Protein Processing, Post-Translational ; drug effects ; Proteins ; metabolism ; RNA, Messenger ; biosynthesis ; genetics ; Receptors, Nicotinic ; biosynthesis ; genetics

Epilepsy is a group of disorders characterized by recurrent seizures. The etiologies of idiopathic epilepsy commonly have a genetic basis. Gene mutations causing several of the inherited epilepsies have been mapped. In this review, the authors summarize the available information on the genetic basis of human epilepsies and epilepsy syndromes, emphasizing how genetic defects may correlate with the pathophysiological mechanisms of brain hyperexcitability and gene defects can lead to epilepsy by altering multiple and diverse aspects of neuronal function.
Epilepsy ; genetics ; Humans ; KCNQ2 Potassium Channel ; Mutation ; NAV1.1 Voltage-Gated Sodium Channel ; Nerve Tissue Proteins ; genetics ; Potassium Channels ; genetics ; Potassium Channels, Voltage-Gated ; Receptors, Nicotinic ; genetics ; Research ; trends ; Research Design ; Sodium Channels ; genetics ; Voltage-Gated Sodium Channel beta-1 Subunit