Variants in the transcriptional corepressor BCORL1 are associated with an X-linked disorder of intellectual disability, dysmorphic features, and behavioral abnormalities

Anju Shukla, Katta M. Girisha, Puneeth H. Somashekar, Sheela Nampoothiri, Rebecca McClellan, Hilary J. Vernon

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)870-874
Number of pages5
JournalAmerican Journal of Medical Genetics, Part A
Volume179
Issue number5
DOIs
Publication statusPublished - 01-05-2019

Fingerprint

Co-Repressor Proteins
Intellectual Disability
Exome
Histone Deacetylases
Germ-Line Mutation
Pedigree
Epigenomics
Computer Simulation
Virulence
Phenotype
Mutation
Genes
Neoplasms
Proteins

All Science Journal Classification (ASJC) codes

  • Genetics(clinical)

Cite this

@article{500cc3d1e6f641a1a139b0538dc30cc8,
title = "Variants in the transcriptional corepressor BCORL1 are associated with an X-linked disorder of intellectual disability, dysmorphic features, and behavioral abnormalities",
abstract = "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.",
author = "Anju Shukla and Girisha, {Katta M.} and Somashekar, {Puneeth H.} and Sheela Nampoothiri and Rebecca McClellan and Vernon, {Hilary J.}",
year = "2019",
month = "5",
day = "1",
doi = "10.1002/ajmg.a.61118",
language = "English",
volume = "179",
pages = "870--874",
journal = "American Journal of Medical Genetics",
issn = "0148-7299",
publisher = "Wiley-Liss Inc.",
number = "5",

}

Variants in the transcriptional corepressor BCORL1 are associated with an X-linked disorder of intellectual disability, dysmorphic features, and behavioral abnormalities. / Shukla, Anju; Girisha, Katta M.; Somashekar, Puneeth H.; Nampoothiri, Sheela; McClellan, Rebecca; Vernon, Hilary J.

In: American Journal of Medical Genetics, Part A, Vol. 179, No. 5, 01.05.2019, p. 870-874.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Variants in the transcriptional corepressor BCORL1 are associated with an X-linked disorder of intellectual disability, dysmorphic features, and behavioral abnormalities

AU - Shukla, Anju

AU - Girisha, Katta M.

AU - Somashekar, Puneeth H.

AU - Nampoothiri, Sheela

AU - McClellan, Rebecca

AU - Vernon, Hilary J.

PY - 2019/5/1

Y1 - 2019/5/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85063803444&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85063803444&partnerID=8YFLogxK

U2 - 10.1002/ajmg.a.61118

DO - 10.1002/ajmg.a.61118

M3 - Article

VL - 179

SP - 870

EP - 874

JO - American Journal of Medical Genetics

JF - American Journal of Medical Genetics

SN - 0148-7299

IS - 5

ER -