Mirzaa et al., 2025 described 35 individuals from 26 families with de novo or maternally-inherited variants in the SMARCA1 gene presenting with an X-linked neurodevelopmental disorder characterized by mild to severe developmental delay/intellectual disability, delayed or regressive speech development, behavioral abnormalities, facial dysmorphisms, and other variable features, including macrocephaly; almost one-third of patients (31%; 11/35) received an ASD diagnosis. Mirzaa et al., 2025 also demonstrated that individuals with SMARCA1 truncating variants exhibited a mildly unique genome-wide DNA methylation profile with a high penetrance of macrocephaly, while genetic dissection of the NURF complex using single and double knockouts of Smarca1 and other NURF complex genes demonstrated the importance of NURF compositon and dosage for proper forebrain development. Damaging de novo missense variants in the SMARCA1 gene have also been identified in a female ASD proband from the SPARK cohort (Zhou et al., 2022), as well as in a severely autistic Portuguese female with a clinical presentation significantly overlapping Rett syndrome (Lopes et al., 2016).
Molecular Function
This gene encodes a member of the SWI/SNF family of proteins. The encoded protein is an ATPase which is expressed in diverse tissues and contributes to the chromatin remodeling complex that is involved in transcription. The protein may also play a role in DNA damage, growth inhibition and apoptosis of cancer cells.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Pathogenic variants in SMARCA1 cause an X-linked neurodevelopmental disorder modulated by NURF complex composition
