title: Dose dependent expression of HDAC4 causes variable expressivity in a novel inherited case of brachydactyly mental retardation syndrome.
abstract: 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.
authors: Department of Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, Richmond, Virginia 23298, USA.
authors: Benjamin
authors: B
authors: Morris
authors: Cécile
authors: C
authors: Etoubleau
authors: Sylvie
authors: S
authors: Bourthoumieu
authors: Sandrine
authors: S
authors: Reynaud-Perrine
authors: Cécile
authors: C
authors: Laroche
authors: Aziza
authors: A
authors: Lebbar
authors: Catherine
authors: C
authors: Yardin
authors: Sarah H
authors: SH
authors: Elsea
mesh_terms: D000293:Adolescent; D059327:Brachydactyly / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D006655:Histone Deacetylases / Q000235:genetics*; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D012097:Repressor Proteins / Q000235:genetics*; D013577:Syndrome
chemical_list: D012097:Repressor Proteins; C400300:HDAC4 protein, human; D006655:Histone Deacetylases