Novel and de novo mutation of PCDH19 in Girls Clustering Epilepsy

Abstract

Background PCDH19 has become the second most relevant gene in epilepsy after SCN1A. Seizures often provoked by fever.MethodsWe screened 152 children with fever‐sensitive epilepsy for gene detection. Their clinical information was followed up.ResultsWe found eight PCDH19 point mutations (four novel and four reported) and one whole gene deletion in 10 female probands (seven sporadic cases and three family cases) who also had cluster seizures. The common clinical features of 16 patients in 10 families included fever‐sensitive and cluster seizures, mainly focal or tonic‐clonic seizures, and absence of status epilepticus, normal intelligence, or mild‐to‐moderate cognitive impairment, the onset age ranges from 5 months to 20 years. Only four patients had multiple or focal transient discharges in interictal EEG. Focal seizures originating in the frontal region were recorded in four patients, two from the parietal region, and one from the occipital region.Conclusion PCDH19 mutation can be inherited or de novo. The clinical spectrum of PCDH19 mutation includes PCDH19 Girls Clustering Epilepsy with or without mental retardation, psychosis, and asymptomatic male. The onset age of PCDH19 Girls Clustering Epilepsy can range from infancy to adulthood. Sisters in the same family may be sensitive to the same antiepileptic drugs. And our report expands the mutation spectrum of PCDH19 Girls Clustering Epilepsy.

The Broad Clinical Spectrum of Epilepsies Associated With Protocadherin 19 Gene Mutation

“…Currently, different drug associations have been tested and none has definitively proven to be superior ( Table 1 ). However, familiar mutations show the same reactivity to antiseizure medication (ASM), therefore the pharmacological choice can be oriented in cases of affected patients in the same family ( 50 ). Despite DS, the use of sodium channel blockers such as lamotrigine and carbamazepine in PCDH-19-related epilepsy has shown less seizure exacerbation ( 22 ).…”

“…With a better knowledge of the clinical presentation, it is now possible to recognize GEFS+ even outside a family context when de novo mutations in the GEFS+ gene are found (36). Several genes mutations are described underlying GEFS+ (37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48) including PCDH19 (49,50). SCN1A is the most commonly involved gene, whose mutations are identified in 19% of affected families (30,37).…”

A Rat Model of a Focal Mosaic Expression of PCDH19 Replicates Human Brain Developmental Abnormalities and Behaviors

“…Interestingly, most of the mutations of PCDH19 in EIEE9 people are related to extracellular domains responsible for the interactions with partner cells (Yang et al 2019) .…”

Epilepsy surgery in PCDH 19 related developmental and epileptic encephalopathy: A case report

“…PCDH19 (Protocadherin19) is a common and important epilepsy related gene, located on the X chromosome, with phenotypic heterogeneity and incomplete penetrance [42] , [34] , [14] , [25] , [7] , [35] . The condition is attributed to pathogenic loss-of-function variants in the PCDH19 gene.…”