Abstract
Juvenile myoclonic epilepsy (JME) is the most prevalent and genetically heterogeneous form of epilepsy and accounts for 10–30% of all the cases worldwide. Ef-hand domain- (c-terminal-) containing protein 1 (EFHC1) encodes for a nonion channel protein and mutations in this gene have been extensively reported in different populations to play a causative role in JME. Linkage between JME and 6p11-12 locus has already been confirmed in Mexican and Dutch families. A case-control study was conducted on Pakistani JME patients for the first time, aimed at finding out EFHC1 mutations that have been reported in different populations. For this purpose, 66 clinically diagnosed JME patients and 108 control subjects were included in the study. Blood samples were collected from all the participants, and DNA was isolated from the lymphocytes by the modified organic method. Total 3 exons of EFHC1, harboring extensively reported mutations, were selected for genotypic analysis. We identified three heterozygous variants, R159W, V460A, P436P, and one insertion in the current study. V460A, an uncommon variant identified herein, has recently been reported in public databases in an unphenotyped American individual. This missense variant was found in 3 Pakistani JME patients from 2 unrelated families. However, in silico analysis showed that V460A may possibly be a neutral variant. While the absence of a majority of previously reported mutations in our population suggests that most of the mutations of EFHC1 are confined to particular ethnicities and are not evenly distributed across the world. However, to imply the causation, the whole gene and larger number of JME patients should be screened in this understudied population.
Highlights
Juvenile myoclonic epilepsy (JME) is the most prevalent form of genetic generalized epilepsy and accounts for at least 10–30% of all epilepsies [1, 2]
JME is typified by myoclonic jerks that predominantly occur after waking, generalized tonic–clonic (GTC) seizures, and infrequent absence seizures [4]
JME prevalence has not yet been evaluated in Pakistan, but on the base of our experience of blood sampling for JME patients, we can presume that JME has a lower prevalence compared to other idiopathic epilepsies in this Asian region
Summary
Juvenile myoclonic epilepsy (JME) is the most prevalent form of genetic generalized epilepsy and accounts for at least 10–30% of all epilepsies [1, 2]. JME alone is responsible for 2 million cases in India [3]. No epidemiological data of JME is present for Pakistan, so the exact prevalence is not known yet. JME is typified by myoclonic jerks that predominantly occur after waking, generalized tonic–clonic (GTC) seizures, and infrequent absence seizures [4]. Epileptologists follow the varied criteria for JME diagnosis but the key diagnostic feature, according to all epileptologists is the same that all JME patients experience myoclonic seizures with or without GTCS and absence seizure in the early morning. Typical EEG symptom for JME is considered as polyspike wave pattern of >4 Hz with normal background activity. Seizures are well controlled when the patient follows the prescription on regular basis but upon discontinuation of medication, a high recurrence rate has been reported in various studies [5, 6]
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