Three Reportedly Unrelated Families With Liddle Syndrome Inherited From a Common Ancestor

Luca Pagani, Yoan Diekmann, Marco Sazzini, Sara De Fanti, Maurizio Rondinelli, Enrico Farnetti, Bruno Casali, Amelia Caretto, Francesca Novara, Orsetta Zuffardi, Paolo Garagnani, Franco Mantero, Mark G Thomas, Donata Luiselli, Ermanno Rossi

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Liddle syndrome is considered a rare Mendelian hypertension. We have previously described 3 reportedly unrelated families, native of an Italian area around the Strait of Messina, carrying the same mutation (βP617L) of the epithelial sodium channel. The aims of our study were (1) to evaluate whether a close genomic relationship exists between the 3 families through the analysis of mitochondrial DNA and Y chromosome; and (2) to quantify the genomic relatedness between the patients with Liddle syndrome belonging to the 3 families and assess the hypothesis of a mutation shared through identity by descent. HVRI (the hypervariable region I) of the mitochondrial DNA genome and the Y chromosome short tandem repeats profiles were analyzed in individuals of the 3 families. Genotyping 542 585 genome-wide single nucleotide polymorphisms was performed in all the patients with Liddle syndrome of the 3 families and some of their relatives. A panel of 780 healthy Italian adult samples typed for the same set of markers was used as controls. espite different lineages between the 3 families based on the analysis of mitochondrial DNA and Y chromosome, the 3 probands and their 6 affected relatives share the same ≈5 Mbp long haplotype which encompasses the mutant allele. Using an approach based on coalescent theory, we estimate that the 3 families inherited the mutant allele from a common ancestor ≈13 generations ago and that such an ancestor may have left ≈20 carriers alive today. The prevalence of Liddle syndrome in the region of origin of the 3 families may be much higher than that estimated worldwide.

Original languageEnglish
Pages (from-to)273-279
Number of pages7
Issue number2
Publication statusPublished - Feb 2018


  • Journal Article


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