Reclassification of the GRIA3 splice-site variant in an X-linked family with intellectual disability and psychiatric symptoms.

A novel GRIA3 splice-site variant causes intellectual disability and psychiatric symptoms, expanding the phenotypic spectrum in an X-linked family.

• Why it matters: Understanding the genetic basis of neurodevelopmental disorders is crucial for accurate diagnosis and counseling, especially for variants of uncertain significance.
• What they did: Researchers identified a new splicing variant (c.268 + 1G>C) in GRIA3 through whole exome sequencing and co-segregation analysis in a family with affected members, confirmed exon skipping with minigene assays, and reclassified the variant as "likely pathogenic" based on ACMG guidelines.
• The result: This finding broadens the clinical presentation associated with GRIA3 mutations, supports improved genetic counseling, and enhances the genetic database for better diagnosis and prenatal planning.