Novel RORA Variants Reveal Genotype–Phenotype Diversity and Variable Expressivity in Neurodevelopmental Disorders

Three distinct RORA variants were identified in four individuals from three unrelated families.

• A 15q21.2-q22.2 deletion encompassing RORA was one of the variants identified.
• A de novo nonsense variant c.499C>T (p.Gln167*) was confirmed in one individual.
• A novel heterozygous frameshift variant c.683_686del (p.Glu228Valfs*78) was found to segregate within a family.
• Clinical presentations varied widely, from severe neurodevelopmental delay and epilepsy to mild intellectual disability and behavioral issues.
• The same frameshift variant showed different phenotypes within a family, illustrating variable expressivity in RORA-related disorders.
• These findings expand the understanding of the genetic and clinical spectrum associated with RORA-related neurodevelopmental disorders.

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