In addition, we show that several PCDH19-FE missense mutations localize to the adhesive interface and abolish Pcdh19 adhesion in <i>in vitro</i> assays, thus revealing the biochemical basis of their pathogenic effects during brain development.
Protocadherin 19 (PCDH19) female limited epilepsy (PCDH19-FE; also known as epilepsy and mental retardation limited to females, EFMR; MIM300088) is an infantile onset epilepsy syndrome with or without intellectual disability (ID) and autism.
Underlying causes were identified in 15 children (65%) and included SCN1A-related Dravet syndrome (formerly severe myoclonic epilepsy of infancy) or genetic epilepsy with febrile seizures plus syndrome (n = 8 and n = 1, respectively), a protocadherin 19 mutation, a 1qter microdeletion, neuronal migration disorders (n = 2), and other monogenic familial epilepsy (n = 2).
These results suggest that PCDH19 plays a major role in epileptic encephalopathies, with a clinical spectrum overlapping that of DS.This disorder mainly affects females.
PCDH19 is expressed in developing brains of human and mouse and is the first member of the cadherin superfamily to be directly implicated in epilepsy or mental retardation.
They include well-recognized syndromes such as tuberous sclerosis complex, epilepsy associated with Rett syndrome, some of the progressive myoclonic epilepsies, and novel disorders such as epilepsy associated with mutations in the PCDH 19 gene.
Additionally, a heterozygous c.2926G>A (Asp976Asn) of PCDH19 was identified in patient with PIGV mutations, the causative gene of Epilepsy and mental retardation limited to females (EFMR).
PCDH19 was analyzed in 159 Japanese female patients with early-onset epilepsy via direct sequencing and multiplex ligation-dependent probe amplification (MLPA) analysis.
The occurrence of epilepsy with mental retardation limited to females (EFMR; MIM 300088) has been recently associated to mutations in the PCDH19 gene, located on chromosome X and encoding for protocadherin 19.