Gardos channelopathy: functional analysis of a novel KCNN4 variant

Author:

Fermo Elisa1,Monedero-Alonso David23,Petkova-Kirova Polina4,Makhro Asya5,Pérès Laurent23ORCID,Bouyer Guillaume23,Marcello Anna Paola1,Longo Filomena6ORCID,Graziadei Giovanna7,Barcellini Wilma1,Bogdanova Anna5,Egee Stephane23,Kaestner Lars89,Bianchi Paola1ORCID

Affiliation:

1. Unità Operativa Semplice (UOS) Fisiopatologia delle Anemie, Unità Operativa Complessa (UOC) Ematologia, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Fondazione Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy;

2. Sorbonne Université, CNRS, Integrative Biology of Marine Models, Station Biologique de Roscoff, Roscoff Cedex, France;

3. Laboratoire d’Excellence GR-Ex, Paris, France;

4. Institute of Neurobiology, Bulgarian Academy of Sciences, Sofia, Bulgaria;

5. Red Cell Research Group, Institute of Veterinary Physiology, Vetsuisse Faculty and the Zurich Center for Integrative Human Physiology (ZIHP), University of Zürich, Zürich, Switzerland;

6. Department of Clinical and Biological Sciences, University of Turin, Turin, Italy;

7. UOC Medicina Generale, Department of Internal Medicine, IRCCS Fondazione Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy;

8. Theoretical Medicine and Biosciences, Saarland University, Homburg, Germany; and

9. Experimental Physics, Saarland University, Saarbrücken, Germany

Abstract

Key Points We show that the novel KCNN4 variant p.S314P is a gain-of-function mutation but is less severe than the previously reported p.R352H variant. The clinical heterogeneity, blurred symptoms, and absence of specific diagnostic markers make the diagnosis of Gardos channelopathy challenging.

Publisher

American Society of Hematology

Subject

Hematology

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