De Novo Heterozygous ZFX Frameshift Variant in a Female With an X-Linked Neurodevelopmental Disorder

ZFX (p.Met666Valfs*2, de novo, heterozygous — previously described in a male)

De novo frameshift — haploinsufficiency + transcriptomic analysis (15 target genes identified)

Report of a 20-year-old woman carrying a heterozygous ZFX frameshift variant p.(Met666Valfs2) identified by WGS (previously reported in a male). Phenotype: psychomotor delay, hypotonia, cardiac abnormalities, ASD, mild intellectual disability, absence seizures, sensorineural hearing loss, hyperpigmentation, ophthalmoplegia. Novel manifestations: hypoplasia of the inferior cerebellar vermis, arterial hypoplasia, long palpebral fissures. RNA-seq identifies 15 neurodevelopmental ZFX* target genes.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

Highly variable expressivity among female carriers. This case documents a truncating variant in a woman with an expanded clinical spectrum (cerebellar, vascular, endocrine). To be integrated into genetic counselling and surveillance of female ZFX variant carriers.

female-manifestation expansion +1; de novo +2; functional RNA-seq analysis +2; 1 case +0; phenotypic expansion +1; journal +1