Mutations in the protocadherin-19 (PCDH19) gene (Xq22.1) cause the X-linked syndrome known as developmental and epileptic encephalopathy 9 (DEE9, OMIM # 300088) (Dibbens et al., 2008). DEE9 is characterized by early-onset clustering epilepsy associated with intellectual disability ranging from mild to profound, autism spectrum disorder, and other neuropsychiatric features including schizophrenia, anxiety, attentiondeficit/ hyperactivity, and obsessive or aggressive behaviors. While seizures may become less frequent in adolescence, psychiatric comorbidities persist and often worsen with age (Dibbens et al., 2008; Kolc et al., 2020). Females with heterozygous mutations and males with postzygotic mutations (bona fide mosaic patients) share the typical DEE9 clinical profile. In contrast, males with hemizygous mutations are generally healthy, although some of them may exhibit autistic traits or autism spectrum disorder (Kolc et al., 2020; Chouery et al., 2023). This unique inheritance pattern for an X-linked gene highlights the role of cellular mosaicism, i.e., the coexistence of cells expressing either the wild type or mutant form of PCDH19, as a crucial, though probably not unique, determinant of DEE9 pathogenesis (Dibbens et al., 2008). The calcium-dependent cell adhesion protein PCDH19 is highly expressed in neurons, particularly in the cortex and structures of the limbic system, including the hippocampus, amygdala, and hypothalamus (reviewed in Gerosa et al., 2018). PCDH19 consists of an extracellular domain with cadherin repeats that mediate adhesion, a transmembrane region, and an intracellular C-terminus (Dibbens et al., 2008; Gerosa et al., 2018).

The complex role of protocadherin-19 in brain function: a focus on the oxytocin system

Mazzoleni, Sara;Busnelli, Marta;Bassani, Silvia
2024

Abstract

Mutations in the protocadherin-19 (PCDH19) gene (Xq22.1) cause the X-linked syndrome known as developmental and epileptic encephalopathy 9 (DEE9, OMIM # 300088) (Dibbens et al., 2008). DEE9 is characterized by early-onset clustering epilepsy associated with intellectual disability ranging from mild to profound, autism spectrum disorder, and other neuropsychiatric features including schizophrenia, anxiety, attentiondeficit/ hyperactivity, and obsessive or aggressive behaviors. While seizures may become less frequent in adolescence, psychiatric comorbidities persist and often worsen with age (Dibbens et al., 2008; Kolc et al., 2020). Females with heterozygous mutations and males with postzygotic mutations (bona fide mosaic patients) share the typical DEE9 clinical profile. In contrast, males with hemizygous mutations are generally healthy, although some of them may exhibit autistic traits or autism spectrum disorder (Kolc et al., 2020; Chouery et al., 2023). This unique inheritance pattern for an X-linked gene highlights the role of cellular mosaicism, i.e., the coexistence of cells expressing either the wild type or mutant form of PCDH19, as a crucial, though probably not unique, determinant of DEE9 pathogenesis (Dibbens et al., 2008). The calcium-dependent cell adhesion protein PCDH19 is highly expressed in neurons, particularly in the cortex and structures of the limbic system, including the hippocampus, amygdala, and hypothalamus (reviewed in Gerosa et al., 2018). PCDH19 consists of an extracellular domain with cadherin repeats that mediate adhesion, a transmembrane region, and an intracellular C-terminus (Dibbens et al., 2008; Gerosa et al., 2018).
2024
Istituto di Neuroscienze - IN - Sede Secondaria Milano
PCDH19, oxytocin, Developmental and epileptic encephalopathy 9
File in questo prodotto:
File Dimensione Formato  
the_complex_role_of_protocadherin_19_in_brain.575 (1).pdf

accesso aperto

Tipologia: Documento in Pre-print
Licenza: Altro tipo di licenza
Dimensione 1.09 MB
Formato Adobe PDF
1.09 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.14243/510127
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? 0
social impact