Twins With Psychiatric Features and a Nonsense HRAS Variant Affecting Transcript Processing

The document is a case study of twins who have a unique phenotype due to a new HRAS variant that affects RNA splicing. This variant leads to symptoms such as mild intellectual disability, anxiety, psychosis, dysmorphism, short stature, early hair loss, vitamin D deficiency, osteopenia, and hematuria. The HRAS variant affects all HRAS isoforms and results in a cryptic splice site, causing a shift in the reading frame and the preferential expression of HRAS transcripts retaining the alternate IDX exon. The study concludes that HRAS variants affecting transcript processing could lead to a wider clinical spectrum, including neuropsychiatric features. However, more research is needed to fully understand the mechanism and phenotypic variability. The study also highlights the importance of clinical genetic evaluation in patients with atypical psychiatric presentations.