Novel and de novo point and large microdeletion mutation in PRRT2‐related epilepsy

Abstract

Background Point and copy number variant mutations in the PRRT2 gene have been identified in a variety of paroxysmal disorders and different types of epilepsy. In this study, we analyzed the phenotypes and PRRT2‐related mutations in Chinese epilepsy children. Methods A total of 492 children with epilepsy were analyzed by whole exome sequencing (WES) and low‐coverage massively parallel CNV sequencing (CNV‐seq) to find the single nucleotide variants and copy number variations (CNVs). And quantitative polymerase chain reaction was utilized to verify the CNVs. Their clinical information was followed up. Results We found PRRT2‐related mutations in 19 patients (10 males and nine females, six sporadic cases and 13 family cases). Twelve point mutations, four whole gene deletion, and three 16p11.2 deletions were detected. The clinical features of 39 patients in 19 families included one early childhood myoclonic epilepsy (ECME), one febrile seizure (FS), two infantile convulsions with paroxysmal choreoathetosis (ICCA), six paroxysmal kinesigenic dyskinesias (PKD), 12 benign infantile epilepsy (BIE), and 17 benign familial infantile epilepsy (BFIE). All patients had normal brain MRI. Interictal EEG showed only one patient had generalized polyspike wave and five patients had focal transient discharges. Focal seizures originating in the frontal region were recorded in one patient, two from the temporal region, and two from the occipital region. Most patients were treated effectively with VPA or OXC, and the child with myoclonic seizures was not sensitive to antiepileptic drugs. Conclusion PRRT2 mutations can be inherited or de novo, mainly inherited. The clinical spectrum of PRRT2 mutation includes BIE, BFIE, ICCA, PKD, FS, and ECME. The PRRT2‐related mutations contained point mutation, whole gene deletion and 16p11.2 deletions, and large microdeletion mutations mostly de novo. It is the first report of PRRT2 mutation found in ECME. Our report expands the mutation and clinical spectrum of PRRT2‐related epilepsy.

Hemiplegic Migraine Associated With PRRT2 Variations

“…2 Point variations and copy number variants in PRRT2, encoding a protein associated with the exocytosis complex, have been identified in a variety of paroxysmal brain disorders and different types of epilepsy, including benign familial infantile epilepsy (BFIE), infantile convulsions with choreoathetosis (ICCA), and paroxysmal kinesigenic dyskinesia (PKD). 3,4 In 2012, a few patients with PKD and a PRRT2 variation were reported to have typical attacks of hemiplegic migraine (HM). [5][6][7] Subsequently, PRRT2 variants were found in several patients with pure HM.…”

Clinical spectrum and genotype-phenotype correlations in PRRT2 Italian patients

“…PRRT2 is also a major gene accounting for PKD [15,16]. Indeed, the mutation rate for PKD in our cohort is 86%.…”

The Genotype and Phenotype of Proline-Rich Transmembrane Protein 2 Associated Disorders in Chinese Children

“…Yang et al found that the whole PRRT2 gene mutation and the 16p11.2 microdeletion were more likely be de novo ( 19 ) . Unfortunately, the parental derivation of eight patients with whole gene deletions was not available.…”