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Hypertension. 2018 Feb;71(2):273-279. doi: 10.1161/HYPERTENSIONAHA.117.10491. Epub 2017 Dec 11.

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

Author information

1
From the Department of Biology (L.P.) and Endocrinology Unit, Department of Medicine (F.M.), University of Padova, Italy; Estonian Biocentre, Tartu (L.P.); Research Department of Genetics, Evolution and Environment, University College London, United Kingdom (Y.D., M.G.T.); Department of Biological Geological and Environmental Sciences (M.S., S.D.F., D.L.) and Department of Experimental, Diagnostic and Specialty Medicine (P.G.), University of Bologna, Italy; IRCCS Centro Cardiologico Monzino, Milano, Italy (M.R.); Department of Oncology and Advanced Technologies, Laboratory of Molecular Biology (E.F., B.C.) and Department of Internal Medicine (E.R.), IRCCS Santa Maria Nuova Hospital, Reggio Emilia, Italy; Department of Endocrinology and Metabolic Diseases, San Raffaele Scientific Institute, Milano, Italy (A.C.); and Department of Molecular Medicine, University of Pavia, Italy (F.N., O.Z.).
2
From the Department of Biology (L.P.) and Endocrinology Unit, Department of Medicine (F.M.), University of Padova, Italy; Estonian Biocentre, Tartu (L.P.); Research Department of Genetics, Evolution and Environment, University College London, United Kingdom (Y.D., M.G.T.); Department of Biological Geological and Environmental Sciences (M.S., S.D.F., D.L.) and Department of Experimental, Diagnostic and Specialty Medicine (P.G.), University of Bologna, Italy; IRCCS Centro Cardiologico Monzino, Milano, Italy (M.R.); Department of Oncology and Advanced Technologies, Laboratory of Molecular Biology (E.F., B.C.) and Department of Internal Medicine (E.R.), IRCCS Santa Maria Nuova Hospital, Reggio Emilia, Italy; Department of Endocrinology and Metabolic Diseases, San Raffaele Scientific Institute, Milano, Italy (A.C.); and Department of Molecular Medicine, University of Pavia, Italy (F.N., O.Z.). ermannorossi9646@gmail.com.

Abstract

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.

KEYWORDS:

DNA, mitochondrial; Liddle syndrome; aldosterone; epithelial sodium channel; renin

PMID:
29229744
PMCID:
PMC5767121
[Available on 2019-02-01]
DOI:
10.1161/HYPERTENSIONAHA.117.10491
[Indexed for MEDLINE]

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