Journal of Genetics

, 98:5 | Cite as

A novel heterozygous duplication of the SLC12A3 gene in two Gitelman syndrome pedigrees: indicating a founder effect

  • Pavlos Fanis
  • Elisavet Efstathiou
  • Vassos Neocleous
  • Leonidas A. Phylactou
  • Adamos HadjipanayisEmail author
Research Note


Gitelman syndrome is an autosomal recessive salt-wasting tubulopathy caused by mutations in the SLC12A3 gene. A female and a male sibling from two unrelated Greek-Cypriot families presenting with a severe salt-wasting tubulopathy due to compound heterozygous mutations of a novel duplication and a previously reported missense mutation in the SLC12A3 gene are described. Sanger sequencing was used to identify possible mutations in the SLC12A3 gene. For the detection of duplications/conversions and deletions in the same gene, Multiplex ligation probe amplification (MLPA) analysis was performed. Direct sequencing and MLPA analysis of the SLC12A3 gene identified two compound heterozygous mutations in both unrelated probands. Both probands were identified to carry in compound heterozygosity the known p.Met581Lys and a novel heterozygous duplication of exons 9-14 (E9_E14dup). The diagnosis of Gitelman syndrome was made through clinical assessment, biochemical screening and genetic analysis. The identification of the novel SLC12A3 duplication seems to be characteristic of Greek-Cypriot patients and suggests a possible ancestral mutational event that has spread in Cyprus due to a possible founder effect. Testing for Gitelman syndrome probable variants can be performed before proceeding to a full gene sequencing dropping the diagnostic cost. In addition, this report adds to the mutational spectrum observed.


Gitelman syndrome salt-wasting tubulopathy SLC12A3 gene hypokalaemia tubular disorders novel mutation 



We would like to thank the A. G. Leventis Foundation for funding this project.


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Copyright information

© Indian Academy of Sciences 2019

Authors and Affiliations

  • Pavlos Fanis
    • 1
    • 2
  • Elisavet Efstathiou
    • 3
  • Vassos Neocleous
    • 1
    • 2
  • Leonidas A. Phylactou
    • 1
    • 2
  • Adamos Hadjipanayis
    • 3
    • 4
    Email author
  1. 1.Department of Molecular Genetics, Function and TherapyThe Cyprus Institute of Neurology and GeneticsNicosiaCyprus
  2. 2.Cyprus School of Molecular MedicineNicosiaCyprus
  3. 3.Department of PediatricsLarnaca General HospitalLarnacaCyprus
  4. 4.The School of MedicineEuropean University CyprusEgkomiCyprus

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