De novoARHGEF9missense variants associated with neurodevelopmental disorder in females: expanding the genotypic and phenotypic spectrum ofARHGEF9disease in females

Marcello Scala*, Evelien Zonneveld-Huijssoon, Marianna Brienza, Oriano Mecarelli, Annemarie H. van der Hout, Elena Zambrelli, Katherine Turner, Federico Zara, Angela Peron, Aglaia Vignoli, Pasquale Striano

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    4 Citations (Scopus)
    52 Downloads (Pure)

    Abstract

    Individuals harboring pathogenic variants inARHGEF9, encoding an essential submembrane protein for gamma-aminobutyric acid (GABA)-ergic synapses named collybistin, show intellectual disability (ID), facial dysmorphism, behavioral disorders, and epilepsy. Only few affected females carrying large chromosomal rearrangements involvingARHGEF9have been reported so far. Through next-generation sequencing (NGS)-based panels, we identified two single nucleotide variants (SNVs) inARHGEF9in two females with neurodevelopmental features. Sanger sequencing revealed that these variants were de novo. The X-inactivation pattern in peripheral blood cells was random. We report the first affected females harboring de novo SNVs inARHGEF9, expanding the genotypic and phenotypic spectrum ofARHGEF9-related neurodevelopmental disorder in females.

    Original languageEnglish
    Pages (from-to)87-94
    Number of pages8
    JournalNeurogenetics
    Volume22
    Early online date17-Sep-2020
    DOIs
    Publication statusPublished - Mar-2021

    Keywords

    • ARHGEF9
    • De novo
    • Neurodevelopmental disorder
    • Autism spectrum disorder
    • Epilepsy
    • X-inactivation
    • LINKED MENTAL-RETARDATION
    • INTELLECTUAL DISABILITY
    • COLLYBISTIN
    • EPILEPSY

    Cite this