Clinical assessment of five patients with BRWD3 mutation at Xq21.1 gives further evidence for mild to moderate intellectual disability and macrocephaly

Eur J Med Genet. 2014 Apr;57(5):200-6. doi: 10.1016/j.ejmg.2013.12.012. Epub 2014 Jan 22.

Abstract

Truncating mutations of the BRWD3 gene have been reported in two distinct families with in total four patients so far. By using array-CGH, we detected a 74 Kb de novo deletion encompassing exons 11 through 41 of BRWD3 at Xq21.1 in a 20 year old boy presenting with syndromic intellectual disability. In addition, by using exome sequencing, we ascertained a family with a BRWD3 nonsense mutation, p.Tyr1131*, in four males with intellectual disability. We compared the clinical presentation of these five patients to that of the four patients already described in the literature for further delineation of the clinical spectrum in BRWD3-related intellectual disability. The main symptoms are mild to moderate intellectual disability (n = 9/9) with speech delay (n = 8/8), behavioral disturbances (n = 7/8), macrocephaly (n = 7/9), dysmorphic facial features (n = 9/9) including prominent forehead, pointed chin, deep-set eyes, abnormal ears, and broad hands and feet (n = 6/6), and skeletal symptoms (n = 7/7) like pes planus, scoliosis, kyphosis and cubitus valgus.

Keywords: BRWD3; Intellectual disability; Macrocephaly; Xq21.1 deletion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Adult
  • Base Sequence
  • Chromosomes, Human, X
  • Codon, Nonsense
  • DNA Mutational Analysis
  • Genetic Association Studies
  • Humans
  • Intellectual Disability / genetics*
  • Male
  • Megalencephaly / genetics*
  • Pedigree
  • Transcription Factors / genetics*
  • Young Adult

Substances

  • BRWD3 protein, human
  • Codon, Nonsense
  • Transcription Factors