Functional and genetic characterization of two extremely rare cases of Williams-Beuren syndrome associated with chronic granulomatous disease

Eur J Hum Genet. 2013 Oct;21(10):1079-84. doi: 10.1038/ejhg.2012.310. Epub 2013 Jan 23.


Williams-Beuren syndrome (WBS) is a neurodevelopmental disorder with multi-systemic manifestations, caused by a heterozygous segmental deletion of 1.55-1.83 Mb at chromosomal band 7q11.23. The deletion can include the NCF1 gene that encodes the p47(phox) protein, a component of the leukocyte NADPH oxidase enzyme, which is essential for the defense against microbial pathogens. It has been postulated that WBS patients with two functional NCF1 genes are more susceptible to occurrence of hypertension than WBS patients with only one functional NCF1 gene. We now describe two extremely rare WBS patients without any functional NCF1 gene, because of a mutation in NCF1 on the allele not carrying the NCF1-removing WBS deletion. These two patients suffer from chronic granulomatous disease with increased microbial infections in addition to WBS. Interestingly, one of these patients did suffer from hypertension, indicating that other factors than NADPH oxidase in vascular tissue may be involved in causing hypertension.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Alleles
  • Child, Preschool
  • Gene Deletion
  • Granulomatous Disease, Chronic / complications
  • Granulomatous Disease, Chronic / diagnosis
  • Granulomatous Disease, Chronic / genetics*
  • Granulomatous Disease, Chronic / metabolism
  • Humans
  • Male
  • NADPH Oxidases / deficiency*
  • NADPH Oxidases / genetics
  • NADPH Oxidases / metabolism
  • Neutrophils / metabolism
  • Williams Syndrome / complications
  • Williams Syndrome / diagnosis
  • Williams Syndrome / genetics*
  • Williams Syndrome / metabolism


  • NADPH Oxidases
  • neutrophil cytosolic factor 1

Supplementary concepts

  • Granulomatous Disease, Chronic, Autosomal Recessive, Cytochrome B-Positive, Type I