Mutations in the BRWD3 gene cause X-linked mental retardation associated with macrocephaly.
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.
Field, M; Tarpey, PS; Smith, R; Edkins, S; O'Meara, S; Stevens, C; Tofts, C; Teague, J; Butler, A; Dicks, E; Barthorpe, S; Buck, G; Cole, J; Gray, K; Halliday, K; Hills, K; Jenkinson, A; Jones, D; Menzies, A; Mironenko, T; Perry, J; Raine, K; Richardson, D; Shepherd, R; Small, A; Varian, J; West, S; Widaa, S; Mallya, U; Wooster, R; Moon, J; Luo, Y; Hughes, H; Shaw, M; Friend, KL; Corbett, M; Turner, G; Partington, M; Mulley, J; Bobrow, M; Schwartz, C; Stevenson, R; Gecz, J; Stratton, MR; Futreal, PA; Raymond, FL
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