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Dose dependent expression of HDAC4 causes variable expressivity in a novel inherited case of brachydactyly mental retardation syndrome
Author(s) -
Morris Benjamin,
Etoubleau Cécile,
Bourthoumieu Sylvie,
ReynaudPerrine Sandrine,
Laroche Cécile,
Lebbar Aziza,
Yardin Catherine,
Elsea Sarah H.
Publication year - 2012
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.35463
Subject(s) - brachydactyly , hdac4 , phenotype , genetics , autism spectrum disorder , microcephaly , biology , histone deacetylase , hypotonia , medicine , autism , gene , endocrinology , histone , short stature , psychiatry
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. © 2012 Wiley Periodicals, Inc.