Dose dependent expression of HDAC4 causes variable expressivity in a novel inherited case of brachydactyly mental retardation syndrome

Am J Med Genet A. 2012 Aug;158A(8):2015-20. doi: 10.1002/ajmg.a.35463. Epub 2012 Jun 29.


Histone deacetylase 4 (HDAC4) serves important roles in multiple human systems, including neurological, cardiac, and skeletal functions. Mutation or deletion of HDAC4 causes brachydactyly mental retardation syndrome (BDMR), a disorder that includes intellectual disability, behavioral abnormalities, autism spectrum disorder, and craniofacial and skeletal anomalies, including brachydactyly type E. We present a case of familial BDMR, including a parent with mild symptoms of the disorder and a child exhibiting a more severe phenotype. Cytogenetic testing showed a cryptic balanced translocation in the mother that resulted in a 2q37.1 monosomy and a 10q26.1 trisomy in the son. Gene expression analyses demonstrated 67% HDAC4 expression in the mother and 23% HDAC4 expression in the son relative to normal controls, lending evidence to the hypothesis that HDAC4 modulates severity of this disorder in a dosage-dependent manner.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Brachydactyly / genetics*
  • Comparative Genomic Hybridization
  • Histone Deacetylases / genetics*
  • Humans
  • Infant
  • Intellectual Disability / genetics*
  • Male
  • Repressor Proteins / genetics*
  • Syndrome


  • Repressor Proteins
  • HDAC4 protein, human
  • Histone Deacetylases