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

Gerosa, Laura; Francolini, Maura; Bassani, Silvia; Passafaro, Maria

doi:10.1002/dneu.22654

Cited by 38 publications

(43 citation statements)

References 57 publications

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“…These are typically associated with early-onset infantile epileptic encephalopathy, with mental retardation and heat-sensitive recurrent seizures. 39 These similar mutations are also seen in Dravet-like phenotype. 33 The heterozygous pathogenic variants are inherited in an unusual X-linked dominant pattern.…”

Section: Geneticsmentioning

confidence: 56%

“…The gene consists of six exons encoding 1,148 proteins. 39 The major encoded protein is considered a calcium-dependent cell-adhesion protein primarily expressed in the brain and a smaller proportion in the gastrointestinal tract, gonads, fat tissue, and skin. About 150 mutations in PCDH19 gene have been identified resulting in sporadic infantile epileptic encephalopathy.…”

Section: Geneticsmentioning

confidence: 99%

“…38 The clinical syndrome affects heterozygous females and mosaic males. [39][40][41] Interestingly, complete deletion in heterozygous females or homozygous males does not result in epilepsy. 40 Usually, unaffected males serve as carriers and pass this variant to their female offspring.…”

Section: Geneticsmentioning

confidence: 99%

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Febrile Seizure Plus and PCDH19-Related Epilepsy Syndromes

Ali

2019

J Pediatr Epilepsy

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Epilepsy is a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures. Practically, a patient has epilepsy if having two unprovoked seizures more than 24 hours apart, one unprovoked seizure and significant risk of another seizure, or epilepsy syndrome. Seizures induced by fever do not therefore fit this classification. An initial febrile seizure may therefore cause a false sense of security in children who evolve to febrile seizure plus syndromes. Sodium channel defects seem to predominate as the main causative factor for febrile seizure plus syndromes. More severe pathological variants, such as Dravet's syndrome, have phenotypic similarities to other fever-associated epileptic encephalopathies, including those caused by mutations in protocadherin 19 (PCDH19). The clinical presentations, investigational studies, and management of febrile seizure plus syndrome, as well as epilepsies associated with PCDH19 mutations will be reviewed.

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Section: Geneticsmentioning

confidence: 56%

Section: Geneticsmentioning

confidence: 99%

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Febrile Seizure Plus and PCDH19-Related Epilepsy Syndromes

Ali

2019

J Pediatr Epilepsy

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“…To recapitulate the mosaicism effect, mixed WT and mutant/KO cells demonstrated mosaic culture of cells and behaved the same way as KO culture of cells (Homan et al., ). A recent review stated that PCDH19 is a complex protein that is involved in diverse neuronal signaling pathways (Gerosa, Francolini, Bassani, & Passafaro, ).…”

Section: Impact Of Variants On Pcdh19 Functionmentioning

confidence: 99%

A mutation update for the PCDH19 gene causing early-onset epilepsy in females with an unusual expression pattern

et al. 2019

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The PCDH19 gene consists of six exons encoding a 1,148 amino acid transmembrane protein, Protocadherin 19, which is involved in brain development. Heterozygous pathogenic variants in this gene are inherited in an unusual X‐linked dominant pattern in which heterozygous females are affected, while hemizygous males are typically unaffected, although they pass on the pathogenic variant to each affected daughter. PCDH19‐related disorder is known to cause early‐onset epilepsy in females characterized by seizure clusters exacerbated by fever and in most cases, onset is within the first year of life. This condition was initially described in 1971 and in 2008 PCDH19 was identified as the underlying genetic etiology. This condition is the result of pathogenic loss‐of‐function variants that may be de novo or inherited from an affected mother or unaffected father and cellular interference has been hypothesized to be the culprit. Heterozygous females are symptomatic because of the presence of both wild‐type and mutant cells that interfere with one another due to the production of different surface proteins, whereas nonmosaic hemizygous males produce a homogenous population of cells. Here, we review novel pathogenic variants in the PCDH19 gene since 2012 to date, and summarize any genotype‐phenotype correlations.

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“…The remaining are missense mutations, and the missense mutations are concentrated in the extracellular domain of the protein (Kolc et al, 2019). The extracellular domain is essential for the normal function of the original cadherin function (Gerosa, Francolini, Bassani, & Passafaro, 2019). PCDH19 is mainly expressed in nerve tissues at different developmental stages, but its specific function is still unclear.…”

mentioning

confidence: 99%

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

Cited by 38 publications

References 57 publications

Febrile Seizure Plus and PCDH19-Related Epilepsy Syndromes

Febrile Seizure Plus and PCDH19-Related Epilepsy Syndromes

A mutation update for the PCDH19 gene causing early-onset epilepsy in females with an unusual expression pattern

Novel and de novo mutation of PCDH19 in Girls Clustering Epilepsy

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