Autosomal dominant inheritance of Williams-Beuren syndrome in a father and son with haploinsufficiency for FKBP6

Clin Dysmorphol. 2005 Apr;14(2):61-65.

Abstract

Williams-Beuren syndrome (WBS) is a neurodevelopmental microdeletion disorder that usually occurs sporadically due to its location within a highly repetitive genomic region that is unstable and prone to unequal cross-over during meiosis. The consequential loss of chromosomal material includes approximately 1.5 Mb of DNA at 7q11.23. Whilst cases of dominant inheritance have been described in the literature, there have been few reports of molecular confirmation and none have carried out detailed genotyping. We describe a Bulgarian father and son with WBS detected by fluorescent in situ hybridisation (with an elastin gene probe) and loss of heterozygosity mapping using microsatellite markers located in the critical region. These individuals appear to have a common WBS heterozygous deletion, confirming the expected dominant transmission and adding to the few familial cases reported. The deletion includes the gene FKBP6 which has recently been shown to play a role in homologous chromosome pairing in meiosis and male fertility in mouse models. Homozygous Fkbp6 -/- male mice are infertile and our data suggests that haploinsufficiency for FKBP6 does not appear to preclude male fertility in WBS, although male infertility involving this gene has the potential to follow the mouse model as a human autosomal recessive condition.

Publication types

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

MeSH terms

  • Adult
  • Aortic Stenosis, Supravalvular / diagnosis
  • Chromosomes, Human, Pair 7 / genetics
  • Elastin / genetics
  • Facies
  • Fathers
  • Gene Deletion
  • Gene Dosage
  • Genes, Dominant / genetics*
  • Genotype
  • Haplotypes / genetics
  • Humans
  • Intellectual Disability / diagnosis
  • Loss of Heterozygosity / genetics
  • Male
  • Nuclear Family
  • Tacrolimus Binding Proteins / genetics*
  • Williams Syndrome / diagnosis
  • Williams Syndrome / genetics*

Substances

  • FKBP6 protein, human
  • Elastin
  • Tacrolimus Binding Proteins