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Variants in the transcriptional corepressor BCORL1 are associated with an X‐linked disorder of intellectual disability, dysmorphic features, and behavioral abnormalities
Author(s) -
Shukla Anju,
Girisha Katta M.,
Somashekar Puneeth H.,
Nampoothiri Sheela,
McClellan Rebecca,
Ver Hilary J.
Publication year - 2019
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.61118
Subject(s) - corepressor , genetics , biology , epigenetics , exome sequencing , intellectual disability , germline , phenotype , germline mutation , gene , exome , mutation , repressor , transcription factor
BCORL1 , a transcriptional corepressor, is involved in negative gene regulation through associations with several protein complexes including Class II histone deacetylases (HDACs). Acquired somatic mutations in BCORL1 have been implicated in the pathogenesis of several malignancies, but germline mutations of BCORL1 have not been associated with a specific genetic syndrome. We report five individuals from three pedigrees with phenotypes including intellectual disability, behavioral difficulties, and dysmorphic features who were found via whole exome sequencing to have variants in BCORL1 . In silico analysis of these variants strongly suggests pathogenicity. We propose that hemizygous pathogenic variants in BCORL1 underlie a newly identified X‐linked epigenetic syndrome.