Mutations in the BRWD3 Gene Cause X-Linked Mental Retardation Associated with Macrocephaly

• Published in: American journal of human genetics Vol. 81; no. 2; pp. 367 - 374
• Main Authors: Field, Michael, Tarpey, Patrick S., Smith, Raffaella, Edkins, Sarah, O’Meara, Sarah, Stevens, Claire, Tofts, Calli, Teague, Jon, Butler, Adam, Dicks, Ed, Barthorpe, Syd, Buck, Gemma, Cole, Jennifer, Gray, Kristian, Halliday, Kelly, Hills, Katy, Jenkinson, Andrew, Jones, David, Menzies, Andrew, Mironenko, Tatiana, Perry, Janet, Raine, Keiran, Richardson, David, Shepherd, Rebecca, Small, Alexandra, Varian, Jennifer, West, Sofie, Widaa, Sara, Mallya, Uma, Wooster, Richard, Moon, Jenny, Luo, Ying, Hughes, Helen, Shaw, Marie, Friend, Kathryn L., Corbett, Mark, Turner, Gillian, Partington, Michael, Mulley, John, Bobrow, Martin, Schwartz, Charles, Stevenson, Roger, Gecz, Jozef, Stratton, Michael R., Andrew Futreal, P., Lucy Raymond, F.
• Format: Journal Article
• Language: English
• Published: Chicago, IL Elsevier Inc 01.08.2007; University of Chicago Press; Cell Press; American Society of Human Genetics
• Subjects: Abnormalities, Multiple - genetics; Adult and adolescent clinical studies; Biological and medical sciences; Chromosomes; Congenital diseases; Fundamental and applied biological sciences. Psychology; General aspects. Genetic counseling; Genes; Genetics of eukaryotes. Biological and molecular evolution; Genotype & phenotype; Head - abnormalities; Humans; Intellectual deficiency; Male; Medical genetics; Medical sciences; Mental Retardation, X-Linked - genetics; Molecular and cellular biology; Mutation; Pedigree; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Sequence Alignment; Transcription Factors - genetics; Human; Sex linked character; Association; Gene; Intellectual deficiency; Genetics; Developmental disorder; X-Chromosome; Mutation; Mental retardation; Macrocephaly; Genetic disease
• ISSN: 0002-9297; 1537-6605
• DOI: 10.1086/520677

In the course of systematic screening of the X-chromosome coding sequences in 250 families with nonsyndromic X-linked mental retardation (XLMR), two families were identified with truncating mutations in BRWD3, a gene encoding a bromodomain and WD-repeat domain–containing protein. In both families, the mutation segregates with the phenotype in affected males. Affected males have macrocephaly with a prominent forehead, large cupped ears, and mild-to-moderate intellectual disability. No truncating variants were found in 520 control X chromosomes. BRWD3 is therefore a new gene implicated in the etiology of XLMR associated with macrocephaly and may cause disease by altering intracellular signaling pathways affecting cellular proliferation.