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Case Reports
. 2021 Mar;22(1):87-94.
doi: 10.1007/s10048-020-00622-5. Epub 2020 Sep 17.

De novo ARHGEF9 missense variants associated with neurodevelopmental disorder in females: expanding the genotypic and phenotypic spectrum of ARHGEF9 disease in females

Marcello Scala  1   2 , Evelien Zonneveld-Huijssoon  3 , Marianna Brienza  4 , Oriano Mecarelli  4 , Annemarie H van der Hout  3 , Elena Zambrelli  5 , Katherine Turner  5 , Federico Zara  6   7 , Angela Peron  8   9   10 , Aglaia Vignoli  8   9 , Pasquale Striano  11   6
Affiliations
Case Reports

De novo ARHGEF9 missense variants associated with neurodevelopmental disorder in females: expanding the genotypic and phenotypic spectrum of ARHGEF9 disease in females

Marcello Scala et al. Neurogenetics. 2021 Mar.

Abstract

Individuals harboring pathogenic variants in ARHGEF9, 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 involving ARHGEF9 have been reported so far. Through next-generation sequencing (NGS)-based panels, we identified two single nucleotide variants (SNVs) in ARHGEF9 in 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 in ARHGEF9, expanding the genotypic and phenotypic spectrum of ARHGEF9-related neurodevelopmental disorder in females.

Keywords: ARHGEF9; Autism spectrum disorder; De novo; Epilepsy; Neurodevelopmental disorder; X-inactivation.

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References

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