Familial periodic paralysis (FPP) is inherited as a dominant trait, and the intermittent failure to maintain the skeletal muscle resting potential is due to mutations in the genes coding for the voltage-gated ion channels. Because several variants of FPP have been delineated on the bases of clinical features, the expectation was that these variants might be due to involvement of different classes of ion channels. The reality of the situation has proven to be more complicated. Mutation-induced defects in the same channel may give rise to diverse phenotypes (phenotypic heterogeneity) and, conversely, mutation in different channel genes may produce a common phenotype (genetic heterogeneity). Regardless of which type of ion channel is defective, the final common pathway is the depolarization-induced loss of muscle excitability; gain-of-function defect in voltage-gated Na channel may cause myotonia, periodic paralysis or both, clinical features of hyperkalemic periodic paralysis and paramyotonia congenita, and loss-of-function defects in voltage-gated Na and Ca channel and K channel may be responsible for periodic paralysis, cardiac arrhythmia or both in hypokalemic periodic paralysis or Andersen's syndrome, respectively. This review focuses on the clinical features, molecular genetic defects, and pathophysiologic mechanisms that underlie FPP.
Arrhythmias, Cardiac ; Channelopathies* ; Clinical Coding ; Genetics* ; Hypokalemic Periodic Paralysis ; Ion Channels ; Membrane Potentials ; Molecular Biology ; Muscle, Skeletal ; Myotonia ; Myotonic Disorders ; Paralyses, Familial Periodic* ; Paralysis ; Paralysis, Hyperkalemic Periodic ; Phenotype

Familial hypokalemic periodic paralysis (HOPP) is a rare autosomal-dominant disease characterized by reversible attacks of muscle weakness occurring with episodic hypokalemia. Mutations in the skeletal muscle calcium (CACNA1S) and sodium channel (SCN4A) genes have been reported to be responsible for familial HOPP. Fifty-one HOPP patients from 20 Korean families were studied to determine the relative frequency of the known mutations and to specify the clinical features associated with the identified mutations. DNA analysis identified known mutations in 12 families: 9 (75%) were linked to the CACNA1S gene and 3 (25%) to the SCN4A gene. The Arg528His mutation in the CACNA1S gene was found to be predominant in these 12 families. Additionally, we have detected one novel silent exonic mutation (1950C>T) in the SCN4A gene. As for a SCN4A Arg669His mutation, incomplete penetrance in a woman was observed. Characteristic clinical features were observed both in patients with and without mutations. This study presents comprehensive data on the genotype and phenotype of Korean families with HOPP.
Adolescent ; Adult ; Calcium Channels/*genetics ; Child ; Child, Preschool ; Genotype ; Humans ; Hypokalemic Periodic Paralysis/*genetics ; Infant ; *Mutation ; Phenotype ; Sodium Channels/*genetics

We analyzed the genetic characteristics of coxsackievirus A4 (CV-A4) based on the entire VP1 coding region. Samples were isolated from patients with acute flaccid paralysis (AFP) in Shaanxi, China from 2006 to 2010. We wished to ascertain the predominant genotype and the relationship between CV-A4 infection and AFP. Sixty-eight non-polio enteroviruses were inoculated onto RD cells (to increase the virus titer) and molecular typing was undertaken. The entire VP1 coding region was amplified. Percentage of CV-A4 was 10.3% (7/68). Analyses of genetic identify and creation of phylogenetic trees revealed that CV-A4 could be classified into A, B and C genotypes. Seven CV-A4 strains from Shaanxi and other CV-A4 strains from China formed an independent evolution lineage located in group 4 and belonged to the C2 sub-genotype. These data suggested that CV-A4 strains of sub-genotype C2 were the predominant genotypes in China. These strains co-evolved and co-circulated with those from other provinces in China, so continued monitoring of CV-A4 (by clinical and genetic surveillance) should be enhanced.
China ; Enterovirus A, Human ; classification ; genetics ; isolation & purification ; Enterovirus Infections ; virology ; Genotype ; Humans ; Paralysis ; virology ; Phylogeny ; Viral Proteins ; genetics

Ataxia ; genetics ; physiopathology ; Calcium Channels ; genetics ; physiology ; Epilepsy ; genetics ; physiopathology ; Genetic Diseases, Inborn ; genetics ; physiopathology ; Humans ; Hypokalemic Periodic Paralysis ; genetics ; physiopathology ; Malignant Hyperthermia ; genetics ; physiopathology ; Migraine with Aura ; genetics ; physiopathology ; Myopathy, Central Core ; genetics ; physiopathology ; Ryanodine ; metabolism ; Spinocerebellar Ataxias ; genetics ; physiopathology

Adult ; Female ; Humans ; Hypokalemic Periodic Paralysis ; genetics ; Infant, Newborn ; Male ; NAV1.4 Voltage-Gated Sodium Channel ; genetics ; Pedigree ; Potassium Channels, Voltage-Gated ; genetics ; Young Adult

CHARGE syndrome, first described by Pagon, was named for its six major clinical features. They are: coloboma of the eye, heart defects, atresia of the choanae, retarded growth and development including CNS anomalies, genital hypoplasia and/or urinary tract anomalies, and ear anomalies and/or hearing loss. We experienced three cases of CHARGE syndrome who displayed ocular coloboma, heart defects, retarded growth and development, and external ear anomalies, and we also review the previously reported literature concerning CHARGE syndrome.
Abnormalities, Multiple*/genetics ; Abnormalities, Multiple*/diagnosis ; Brain/abnormalities* ; Case Report ; Child, Preschool ; Choroid/abnormalities* ; Coloboma/genetics ; Coloboma/diagnosis* ; Ear, External/abnormalities ; Entropion/genetics ; Entropion/diagnosis ; Exotropia/genetics ; Exotropia/diagnosis ; Exotropia/congenital ; Facial Paralysis/genetics ; Facial Paralysis/congenital ; Female ; Heart Defects, Congenital/genetics ; Heart Defects, Congenital/diagnosis* ; Human ; Infant ; Karyotyping ; Male ; Mandible/abnormalities* ; Retina/abnormalities* ; Syndrome

OBJECTIVETo report an X-linked dominant Charcot-Marie-Tooth disease (CMTX) Chinese family with vocal cord paresis and to identify the mutation of gap junction protein beta 1 gene (GJB1).

METHODSPart of the family members with dysphagia, dysphonia and lethal respiratory failure were studied through flexible laryngoscope, clinical, brain MRI and electrophysiological examinations. After excluding large fragment tandem duplication containing peripheral myelin protein 22 gene (PMP22), direct sequencing was performed to analyze the mutation of the GJB1 gene in 5 patients including the proband, 5 unaffected family members and 50 unrelated healthy individuals.

RESULTSEight members spanning 3 generations in this family were affected with CMTX characterized by progressive atrophy and weakness of the anterior tibial and peroneal muscles, especially in the proband. Vocal cord paresis was observed through flexible laryngoscope in total of 4 affected members with dysarthria and dysphagia, 2 of them died of severe respiratory failure due to complete bilateral vocal cord involvement. Normal brain MRI was observed in the proband. The electrophysiological data showed predominant demyelization involving the motor and sensory nerves in the proband. DNA sequencing revealed a de novo c.186 C>G missense mutation in exon 2 of the GJB1 gene, the mutation cosegregated with phenotype.

CONCLUSIONRespiratory failure associated with vocal cord involvement may be a rare and severe symptom in CMTX. The present report provides further evidence for clinical and genetic heterogeneity in the X-linked Charcot-Marie-Tooth disease.

Adolescent ; Adult ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Case-Control Studies ; Charcot-Marie-Tooth Disease ; genetics ; Connexins ; genetics ; Female ; Humans ; Male ; Molecular Sequence Data ; Mutation, Missense ; Myelin Proteins ; genetics ; Pedigree ; Vocal Cord Paralysis ; genetics ; Young Adult

OBJECTIVEMutation screening was performed to a Chinese family with hypokalaemic periodic paraiysis(HOKPP) for locating the corresponding mutations of gene and for specifying the clinical features associated with mutations.

METHODSThe cilnical features of patients from HOKPP family were summurized. Techniques of target exon PCR and direct sequencing were used to screen the mutation in CACNA1S and SCN4A genes in all numbers of the family.

RESULTSTwo patients of the family showed the typical features of HOKPP: the age of disease onset is during the childhood, acetazolamide is effective to patients treated. A heterozygous point mutation 3716 (G>A) causing R1239H was found in exon 30 of CACNA1S gene of the patients, but not found in normal members of the family.

CONCLUSIONThe mutant R1239H in CACNA1S gene exists in Chinese patients with familial hypokalaemic periodic paralysis.

Adolescent ; Adult ; Base Sequence ; Calcium Channels ; genetics ; China ; DNA Mutational Analysis ; Family Health ; Female ; Humans ; Hypokalemic Periodic Paralysis ; genetics ; Male ; Mutation ; Pedigree ; Polymerase Chain Reaction

Molecular typing was conducted for three human enteroviruses (HEV) isolated from acute flaccid paralysis (AFP) cases in Shandong province, China. RNAs from virus supernatants were extracted and complete VP1 genes were amplified by RT-PCR and sequenced. Genotypes of these isolates were identified as HEV type 73, 75 and 97, respectively by BLAST program. Homology and phylogenetic tree analyses were performed. Sequence analysis of VP1 gene showed significant variation compared with prototype strains. This study presents the genetic characteristics of HEV 73, 75 and 97 of specie B in Shandong Province, and the first report of HEV97 in China.
Base Sequence ; Cell Line ; China ; Enterovirus ; classification ; genetics ; isolation & purification ; Enterovirus Infections ; virology ; Humans ; Molecular Sequence Data ; Paralysis ; virology ; Phylogeny ; Viral Proteins ; genetics

The present research was aimed to investigate the relationships between the single nueleotide polymorphisms (SNPs) of CACNA1S gene 11 exon and thyrotoxic hypokalemic periodic paralysis (THPP)in the people of Han Nationality in Sichuan China. 100 male subjects were divided into four groups in this study, i.e., 22 patients with THPP, 23 patients with hypokalemic periodic paralysis (HPP), 33 patients with thyrotoxicosis but without hypokalemic periodic paralysis (NTHPP), and 22 healthy (control group) subjects. The sequences of the CACNA1S gene exon 11 polymorphisms, for the four groups respectively, were analysed by the SNPs method with polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and DNA direct sequencing. A meta-analysis of three additional studies was also performed. Three SNPs of exon 11 of the CACNA1S gene (C1491T, T1551C, C1564T) were present in all the four groups. The polymorphisms C1491T and T1551C were present in both homozygotes and heterozygotes, while the C1564T polymorphism was present only in heterozygotes. The genotype frequencies of variants at C1491T and T1551C were not significantly associated with TPP (dominant model: P=0.530 and P=0.568; allele frequency model: P=0.563 and P=0.568). A Meta-analysis yielded combined odds ratio (OR) for TPP of 2. 12 (95% CI: 0.80-5.60) at C1491T, 2.90 (95% CI: 0.71-11.78) at T1551C, and 1.61 (95% CI: 0.36-7.26) at C1564T with the dominant model. These results suggested that three SNPs of CACNA1S gene exon 11 definitely could exist but could not be associated with TPP people of Han Nationality in Sichuan.
Adult ; Base Sequence ; Calcium Channels ; genetics ; China ; ethnology ; Chromosomes, Human, Pair 11 ; genetics ; Exons ; Humans ; Hypokalemic Periodic Paralysis ; etiology ; genetics ; Male ; Molecular Sequence Data ; Polymorphism, Single Nucleotide ; Thyrotoxicosis ; complications ; genetics