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: Benjamin Morris, Cécile Etoubleau, Sylvie Bourthoumieu, Sandrine Reynaud-Perrine, Cécile Laroche, Aziza Lebbar, Catherine Yardin, Sarah H Elsea
• Journal: American journal of medical genetics. Part A (Am J Med Genet A) Vol. 158A Issue 8 Pg. 2015-20 (Aug 2012) ISSN: 1552-4833 [Electronic] United States
• PMID: 22753018 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Wiley Periodicals, Inc.

Chemical References

• Repressor Proteins
• HDAC4 protein, human
• Histone Deacetylases

Topics

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