ABSTRACT
Abnormal expression and dysfunction of voltage-gated Calcium channels (VGCCs) can give rise to a variety of neurological disorders in children, including epilepsy, migraine and ataxia.In the past, only CACNA1A, CACNA1H, CACNA2D2 and CACNB4 were considered associated with epilepsy in children.In recent years, an increasing number of VGCCs gene associated with epilepsy in children have been found, especially developmental and epileptic encephalopathy genes.This study aims to review the research progress of VGCCs gene mutations associated with epilepsy in children.
ABSTRACT
Dravet syndrome is a rare and severe developmental epileptic encephalopathy with variable clinical phenotypes.Dravet syndrome is difficult to diagnose and treat, and related comorbidities have a profound impact on the long-term quality of life of patients and their parents.SCN1A is the main pathogenic gene of Dravet syndrome, and SCN1A mutations are found in more than 85% of the patients.In recent years, with the development of genetic testing technology and the accumulation of cases, the understanding of the characteristics of epileptic seizures, comorbidities and SCN1A gene mutation characteristics in Dravet syndrome has gradually deepened.In addition to conventional antiepileptic drugs, new antiepileptic drugs(cannabidiol, fenfluramine)have also shown good antiepileptic effects and are expected to become second-line drugs for the treatment of Dravet syndrome seizures.This article mainly reviews the research progress of unique clinical phenotype, SCN1A gene mutation characteristics and new antiepileptic drugs of Dravet syndrome, in order to deepen clinicians′ understanding of the disease.
ABSTRACT
<p><b>OBJECTIVE</b>Previous studies have demonstrated that two homozygous missense MYO1E mutations are associated with childhood autosomal recessive focal segmental glomerulosclerosis in steroid-resistant nephrotic syndrome (SRNS) families from Italy and Turkey. Non-disease-causing heterozygous MYO1E variants were also found in other SRNS patient cohorts. However, the role of MYO1E mutations in Chinese sporadic SRNS has not been established.</p><p><b>METHOD</b>Peripheral blood samples were collected for genetic analysis from 54 children with sporadic SRNS in Chinese Han ethnic group and a normal control group of 59 healthy adult volunteers. None of the patients carried mutations in NPHS2 or WT1. Genomic DNA was extracted from peripheral blood leukocytes. Twenty-eight exons and exon-intron boundaries of the MYO1E gene were amplified by polymerase chain reaction. Mutational analysis was performed by direct DNA sequencing and restriction endonuclease digestion.</p><p><b>RESULT</b>Fifty-one variants in the MYO1E gene were identified in 54 children with sporadic SRNS. Among them, 10 MYO1E mutations of IVS1-11T>C, IVS2-86T>A, 279T>C (D93D), IVS6-181G>A, 718C>T (L240F), 1678A>G (T560A), IVS16-35A>G, IVS18+48T>A, IVS19+38G>A and IVS25+13C>T were detected in 11 patients, whereas they were absent in the 59 normal Chinese controls. Forty-one variants in MYO1E were identified and all of them were published in single nucleotide polymorphism database from national center for biotechnology information. Furthermore, all the 10 MYO1E mutations were in heterozygous states.</p><p><b>CONCLUSION</b>MYO1E mutations are not a major cause of Chinese children with sporadic SRNS in the study.</p>