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

Kay Metcalfe, Emil Simeonov, William Beckett, Dian Donnai, May Tassabehji

    Research output: Contribution to journalArticlepeer-review

    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 ∼ 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. © 2005 Lippincott Williams & Wilkins.
    Original languageEnglish
    Pages (from-to)61-65
    Number of pages4
    JournalClinical dysmorphology
    Volume14
    Issue number2
    DOIs
    Publication statusPublished - Apr 2005

    Keywords

    • Autosomal dominant inheritance
    • Fertility
    • FKBP6
    • Williams-Beuren syndrome

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