PCDH19 regulation of neural progenitor cell differentiation suggests asynchrony of neurogenesis as a mechanism contributing to PCDH19 Girls Clustering Epilepsy

Homan, Claire C.; Pederson, Stephen; To, Thu Hien; Tan, Chuan; Piltz, Sandra; Corbett, Mark; Wolvetang, Ernst J.; Thomas, Paul Q.; Jolly, Lachlan A.; Gécz, Jozef

doi:10.1016/j.nbd.2018.05.004

Cited by 47 publications

(64 citation statements)

References 75 publications

(55 reference statements)

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“…4,13,14 The psychiatric features in childhood and adolescence of severe behavioral problems, obsessional features, and ASD often prove more disabling for patients and families, even though seizures may have abated. The term PCDH19 Girl Clustering Epilepsy has been recently suggested to aid in earlier recognition of this serious disorder.…”

Section: Discussionmentioning

confidence: 99%

“…The term PCDH19 Girl Clustering Epilepsy has been recently suggested to aid in earlier recognition of this serious disorder. 4,13,14 The psychiatric features in childhood and adolescence of severe behavioral problems, obsessional features, and ASD often prove more disabling for patients and families, even though seizures may have abated. 1 Here, we have described 8 females with PCDH19-GCE who present with adolescent-or adult-onset psychotic disorder with prominent decline in functioning, of whom 6 satisfied a diagnosis of schizophrenia.…”

Section: Discussionmentioning

confidence: 99%

“…4,13,14 We examined whether each female had experienced psychosis and serious behavioral problems and the evolution of these symptoms over time. 4,13,14 We examined whether each female had experienced psychosis and serious behavioral problems and the evolution of these symptoms over time.…”

Section: Phenotypingmentioning

confidence: 99%

“…We use the term "PCDH19-Girls Clustering Epilepsy" (or PCDH19-GCE) for the well-recognized epilepsy syndrome associated with PCDH19 pathogenic variants, as suggested previously. 4,13,14 We examined whether each female had experienced psychosis and serious behavioral problems and the evolution of these symptoms over time. We also evaluated the epilepsy phenotype, developmental course and intellect, magnetic resonance imaging (MRI) findings, genetic results, and the family history.…”

Section: Phenotypingmentioning

confidence: 99%

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Schizophrenia is a later‐onset feature ofPCDH19Girls Clustering Epilepsy

et al. 2019

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Summary Objective To investigate the occurrence of psychosis and serious behavioral problems in females with protocadherin 19 gene (PCDH19) pathogenic variants. Methods We evaluated whether psychosis and serious behavioral problems had occurred in 60 females (age 2‐75 years) with PCDH19 pathogenic variants belonging to 35 families. Patients were identified from epilepsy genetics databases in Australia, New Zealand, the United States, and Canada. Neurologic and psychiatric disorders were diagnosed using standard methods. Results Eight of 60 females (13%) from 7 families developed a psychotic disorder: schizophrenia (6), schizoaffective disorder (1), or an unspecified psychotic disorder (1). Median age at onset of psychotic symptoms was 21 years (range 11‐28 years). In our cohort of 39 females aged 11 years or older, 8 (21%) developed a psychotic disorder. Seven had ongoing seizures at onset of psychosis, with 2 continuing to have seizures when psychosis recurred. Psychotic disorders occurred in the setting of mild (4), moderate (2), or severe (1) intellectual disability, or normal intellect (1). Preexisting behavioral problems occurred in 4 patients, and autism spectrum disorder in 3. Two additional females (3%) had psychotic features with other conditions: an adolescent had recurrent episodes of postictal psychosis, and a 75‐year‐old woman had major depression with psychotic features. A further 3 adolescents (5%) with moderate to severe intellectual disability had onset of severe behavioral disturbance, or significant worsening. Significance We identify that psychotic disorders, including schizophrenia, are a later‐onset manifestation of PCDH19 Girls Clustering Epilepsy. Affected girls and women should be carefully monitored for later‐onset psychiatric disorders.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Phenotypingmentioning

confidence: 99%

Section: Phenotypingmentioning

confidence: 99%

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Schizophrenia is a later‐onset feature ofPCDH19Girls Clustering Epilepsy

et al. 2019

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“…As mentioned above, perturbation of cell adhesion affinities, due to PCDH19 loss, affected zebrafish optical tectum architecture (Biswas et al , ; Cooper et al , ; Emond et al , ). Furthermore, loss of PCDH19 results in migration impairment, increased neurogenesis and loss of polarity both in human neural stem cells and in cultured neurons derived from Pcdh19 null mice (Homan et al , ). Other studies on Pcdh19 null mice show both increased and abnormal neuronal mobility, resulting in impairment in neuronal migration (Pederick et al , ).…”

Section: Mutations In Pcdh19 Gene and Encephalopathiesmentioning

confidence: 99%

The Role of Protocadherin 19 (PCDH19) in Neurodevelopment and in the Pathophysiology of Early Infantile Epileptic Encephalopathy‐9 (EIEE9)

Gerosa

Francolini

Bassani

et al. 2019

Developmental Neurobiology

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PCDH19 is considered one of the most clinically relevant genes in epilepsy, second only to SCN1A. To date about 150 mutations have been identified as causative for PCDH19‐female epilepsy (also known as early infantile epileptic encephalopathy‐9, EIEE9), which is characterized by early onset epilepsy, intellectual disabilities, and behavioral disturbances. Although little is known about the physiological role of PCDH19 and the pathogenic mechanisms that lead to EIEE9, in this review, we will present latest researches focused on these aspects, underlining protein expression, its known functions and the mechanisms by which the protein acts, with particular interest in PCDH19 extracellular and intracellular roles in neurons.

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Novel and de novo mutation of PCDH19 in Girls Clustering Epilepsy

Liu

et al. 2019

Brain and Behavior

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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.

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PCDH19 regulation of neural progenitor cell differentiation suggests asynchrony of neurogenesis as a mechanism contributing to PCDH19 Girls Clustering Epilepsy

Cited by 47 publications

References 75 publications

Schizophrenia is a later‐onset feature ofPCDH19Girls Clustering Epilepsy

Schizophrenia is a later‐onset feature ofPCDH19Girls Clustering Epilepsy

The Role of Protocadherin 19 (PCDH19) in Neurodevelopment and in the Pathophysiology of Early Infantile Epileptic Encephalopathy‐9 (EIEE9)

Novel and de novo mutation of PCDH19 in Girls Clustering Epilepsy

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