An ancestral variant causing type I xanthinuria in Turkmen and Arab families is predicted to prevail in the Afro-Asian stone-forming belt

Hava Peretz, Michael Korostishevsky, David M. Steinberg, Mustafa Kabha, Sali Usher, Irit Krause, Hannah Shalev, Daniel Landau, David Levartovsky

    Research output: Contribution to journalArticlepeer-review

    1 Scopus citations

    Abstract

    Classical xanthinuria is a rare autosomal recessive metabolic disorder characterized by lack of xanthine dehydrogenase activity that often manifests as xanthine urolithiasis and risk of drug toxicity. Variants in the XDH or HMCS gene underlie classical xanthinuria type I and type II, respectively. Here we present two Israeli Arab families affected by type I xanthinuria in whom a c.2164A>T (Lys722Ter) variant in the XDH gene, previously reported in a Turkish family of Turkmen origin, was identified. Analysis of polymorphic markers surrounding the variant site revealed common haplotypes spanning 0.6 Mbp shared by all three, and 1.7 Mbp shared by two of the studied families. By applying Bayesian methods to a simple model of crossover events through generations in the chromosomes carrying the variant, the most recent common ancestor of these families was found to be 179 (95% credible limit 70) generations old. The estimated antiquity of the variant, the historical genealogy of the affected families and the history and present day dispersion of their people strongly suggest prevalence of this variant in the Afro-Asian stone-forming belt. As far as we are aware, this is a first report of an ancient variant causing xanthinuria with potential wide geographical dispersion.

    Original languageEnglish
    Pages (from-to)45-52
    Number of pages8
    JournalJIMD Reports
    Volume51
    Issue number1
    DOIs
    StatePublished - 1 Jan 2020

    Keywords

    • Afro-Asian stone-forming belt
    • Arabs
    • Turkmens
    • XDH gene
    • ancestral mutation
    • genealogical history
    • time to most recent common ancestor
    • xanthinuria

    ASJC Scopus subject areas

    • Internal Medicine
    • Endocrinology, Diabetes and Metabolism
    • Biochemistry, Genetics and Molecular Biology (miscellaneous)

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