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.(Met666Valfs*2) 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