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

Autor: Shukla A; Department of Medical Genetics, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India., Girisha KM; Department of Medical Genetics, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India., Somashekar PH; Department of Medical Genetics, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India., Nampoothiri S; Department of Paediatric Genetics, Amrita Institute of Medical Sciences & Research Centre, Cochin, India., McClellan R; Department of Neurogenetics, Kennedy Krieger Institute, Baltimore, Maryland., Vernon HJ; Department of Neurogenetics, Kennedy Krieger Institute, Baltimore, Maryland.; Department of Pediatrics, Johns Hopkins University, Baltimore, Maryland.
Jazyk: angličtina
Zdroj: American journal of medical genetics. Part A [Am J Med Genet A] 2019 May; Vol. 179 (5), pp. 870-874. Date of Electronic Publication: 2019 Apr 02.
DOI: 10.1002/ajmg.a.61118
Abstrakt: 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.
(© 2019 Wiley Periodicals, Inc.)
Databáze: MEDLINE
Externí odkaz: