Abstract
BackgroundPoint 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.MethodsA 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.ResultsWe 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.
Highlights
Point and copy number variant mutations in the PRRT2 gene have been identified in a variety of paroxysmal disorders and different types of epilepsy
Mutations in the proline-rich transmembrane protein 2 (PRRT2) gene on chromosome 16 were first identified in the paroxysmal kinesigenic dyskinesias (PKD) family and subsequently in benign familial infantile epilepsy (BFIE) and infantile convulsions with paroxysmal choreoathetosis (ICCA) (Mathot, Lederer, Gerard, Gueulette, & Deprez, 2017; Okumura et al, 2019; Zhao et al, 2019) and were reported to be associated with benign infants myoclonic (Maini et al, 2016), west syndrome (Djemie et al, 2014), febrile convulsions (FS) (Zheng et al, 2016), hemiplegic migraines (Cloarec et al, 2012), intermittent ataxia, and other differential movement disorders (Castelnovo et al, 2016; Delcourt et al, 2015; Ebrahimi-Fakhari et al, 2014; Legris et al, 2019)
Copy number deletions of this gene such as 16p11.2 deletion are known to cause PRRT2-related diseases (Dale, Grattan-Smith, Nicholson, & Peters, 2012; Silveira-Moriyama et al, 2018; Termsarasab et al, 2014; Weber, Kohler, Hahn, Neubauer, & Muller, 2013). 16p11.2 microdeletion syndrome is a kind of congenital gene deletion disease, with the clinical manifestations as autism, developmental delay, mental retardation, spinal deformity, and a series of neuropsychiatric developmental diseases (Al-Jawahiri, Jones, & Milne, 2019; Castelein, Steyaert, Peeters, & van Buggenhout, 2019; Hinkley et al, 2019; Li et al, 2018a; Siu et al, 2019)
Summary
Point and copy number variant mutations in the PRRT2 gene have been identified in a variety of paroxysmal disorders and different types of epilepsy. 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). 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.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
