Presented at IMFAR 2012.
Dravet Syndrome- Genetic Analysis of SCN1A and PCDH19 Mutations for 17 Chinese Children
V. C. N. Wong, A. K. Y. Kwong and C. W. Fung, Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, China
Background: For Dravet syndrome (DS), 80% had mutation in SCN1A gene, which encoded a voltage-gated sodium channel. Recent study demonstrated that 16% of SCN1A-negative patients had mutations in protocadherin-19 (PCDH19) genes.”
Objectives: The present study examined the genetic mutations in Chinese DS children and assesses the relationship between mutation and phenotype.
Methods: DNA of 17 DS in The University of Hong Kong was screened for SCN1A mutation using polymerase chain reaction and direct sequencing. SCN1A-negative female patients were then screened for PCDH19 mutation.
Results: For DS, 82% (14/17) had SCN1A mutations- truncating mutations (6), splice site mutations (2) and missense mutations (6). These mutations affected Nav1.1 protein functions by pathogenicity assessments including conservative, SIFT and Align-GVGD analyses.
We found a relationship between the type of mutation and the degree of intellectual disability (p<0.05), with truncating/ splice site mutations associated with moderate/ severe mental retardation. At the evolution of the disease, 79% (11/14) of DS patients with SCN1A mutations had features which fit into the diagnostic criteria of autism spectrum disorder (ASD). 57% (8/14) had history of vaccination-induced seizures. One of the two female SCN1A-negative patients had PCDH19 mutation.
Conclusions: High percentage of genetic mutations was identified in our Chinese cohort of Dravet Syndrome. Pathogenicity assessment demonstrated that the mutations were linked to the phenotypes of Dravet syndrome. Our detection of high frequency of ASD (79%) and vaccination-induced encephalopathy (57%) in those DS with SCN1A mutation suggested evaluating ASD with epilepsy or vaccination induced encepalopathic children for any relationship between SCN1A mutations.”
Previous research in May 2012
SCNIA Mutation Associated With Intractable Myoclonic Epilepsy and Migraine Headache.
Mutations in the SCN1A gene are associated with a variety of epilepsy syndromes and more recently with familial hemiplegic migraine. The spectrum of phenotypes can be quite broad even within the same family and with the same mutation. Here we describe a child with intractable myoclonic epilepsy and autism spectrum disorder who carries an inherited mutation in SCN1A (c.3521C>G, p.T1174 S). Previous reports suggest this mutation causes familial hemiplegic migraine and interestingly both the patient’s mother, who also carries the mutation, and the patient’s maternal grandmother, have frequent migraines with aura.
Sodium channels SCN1A, SCN2A and SCN3A in familial autism.
Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.
De novo mutations revealed by whole-exome sequencing are strongly associated with autism.
Dravet syndrome: patients with co-morbid SCN1A gene mutations and mitochondrial electron transport chain defects.
Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations.
Epilepsy and the new cytogenetics.
Genetic calcium signaling abnormalities in the central nervous system: seizures, migraine, and autism.
[Autism, epilepsy and genetics]. Spanish Original