Mutations in the HDAC8 gene are responsible for a form of Cornelia de Lange syndrome (Cornelia de Lange syndrome-5; OMIM 300882) (Deardorff et al., 2012; Harakalova et al., 2012; Kaiser et al., 2014; Ansari et al., 2014). A comparison of the primary clinical findings in individuals with molecularly confirmed Cornelia de Lange syndrome in Kline et al., 2018 determined that 20-49% of individuals with HDAC8 mutations presented with autism spectrum disorder. An X-chromosome-wide association study of 6,873 individuals with autism from MSSNG, SSC, and SPARK (5,639 males and 1,234 females) and 8,981 controls (3,911 males and 5,070 females) in Mendes et al., 2025 identified three intronic SNPs in the HDAC8 gene that reached the significance threshold for association in meta-XWAS and both-XWAS analyses; furthermore, rare predicted damaging SNVs (<0.1% frequency in gnomAD) in the HDAC8 gene were found to have a higher frequency in ASD cases (male, female, and both sexes) from MSSNG, SSC, and SPARK compared to other family members in this report.
Molecular Function
The protein encoded by this gene belongs to class I of the histone deacetylase family. It catalyzes the deacetylation of lysine residues in the histone N-terminal tails and represses transcription in large multiprotein complexes with transcriptional co-repressors.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
HDAC8 mutations in Cornelia de Lange syndrome affect the cohesin acetylation cycle.
Comparison of first-tier whole-exome sequencing with a multi-step traditional approach for diagnosing paediatric outpatients: An Italian prospective study
