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.

在ARHGEF9 中携带致病性变异的个体，编码γ-氨基丁酸 (GABA) 的必需亚膜蛋白——名为 collybistin 的能突触，表现出智力障碍 (ID)、面部畸形、行为障碍和癫痫。迄今为止，只有少数携带涉及ARHGEF9 的大染色体重排的受影响女性被报道。通过基于下一代测序 (NGS) 的面板，我们在具有神经发育特征的两名女性的ARHGEF9中发现了两个单核苷酸变异 (SNV) 。Sanger 测序显示这些变异是从头开始的。外周血细胞中的 X 灭活模式是随机的。我们报告了第一个在ARHGEF9 中携带 de novo SNVs 的受影响女性，扩大了女性ARHGEF9相关神经发育障碍的基因型和表型谱。