Multiplex epithelium dysfunction due to CLDN10 mutation: the HELIX syndrome

Smail Hadj-Rabia; Gaelle Brideau; Yasser Al-Sarraj; Rachid Maroun; Marie-Lucile Figueres; Stéphanie Leclerc-Mercier; Eric Olinger; Stéphanie Baron; Catherine Chaussain; Dominique Nochy; Rowaida Taha; Bertrand Knebelmann; Vandana Joshi; Patrick Curmi; Marios Kambouris; Rosa Vargas-Poussou; Christine Bodemer; Olivier Devuyst; Pascal Houillier; Hatem El-Shanti

Multiplex epithelium dysfunction due to CLDN10 mutation: the HELIX syndrome

Smail Hadj-Rabia ^{1, 2} Gaelle Brideau ³ Yasser Al-Sarraj ⁴ Rachid Maroun ⁵ Marie-Lucile Figueres ³ Stéphanie Leclerc-Mercier ^{2, 6} Eric Olinger ⁷ Stéphanie Baron ^{3, 8} Catherine Chaussain ⁹ Dominique Nochy ¹⁰ Rowaida Taha ⁴ Bertrand Knebelmann ¹¹ Vandana Joshi ⁵ Patrick Curmi ⁵ Marios Kambouris ^{4, 12, 13} Rosa Vargas-Poussou ^{14, 3} Christine Bodemer ^{1, 2} Olivier Devuyst ¹⁵ Pascal Houillier ^{3, 8} Hatem El-Shanti ^{4, 16, 17}

1 Service de dermatologie [CHU Necker]

2 IMAGINE - U1163 - Imagine - Institut des maladies génétiques

3 CRC - U1138 - Centre de Recherche des Cordeliers

4 QBRI - Qatar Biomedical Research Institute

5 SABNP - Structure et activité des biomolécules normales et pathologiques

6 Service de pathologie [CHU Necker]

7 Institute of Physiology, University of Zurich, Zurich, Switzerland

8 Service de Physiologie [Georges-Pompidou]

9 Service d'Odontologie [Bretonneau]

10 Département de Pathologie [AP-HP Hôpital Européen Georges Pompidou]

11 Service de néphrologie pédiatrique [CHU Necker]

12 Yale University School of Medicine

13 Sidra Medical and Research Center

14 Service de Génétique [AP-HP Hôpital Européen Georges Pompidou, Paris]

15 Institute of Physiology, University of Zurich, Zurich, Switzerland

16 Department of Pediatrics and Holden Comprehensive Cancer Center [Iowa City, USA]

17 JU - The University of Jordan

Abstract : Purpose:We aimed to identify the genetic cause to a clinicalsyndrome encompassing hypohidrosis, electrolyte imbalance,lacrimal gland dysfunction, ichthyosis, and xerostomia (HELIXsyndrome), and to comprehensively delineate the phenotype.Methods:We performed homozygosity mapping, whole-genomesequencing, gene sequencing, expression studies, functional tests,protein bioinformatics, and histological characterization in twounrelated families with HELIX syndrome.Results:We identified biallelic missense mutations (c.386C>T,p.S131L and c.2T>C, p.M1T) inCLDN10Bin six patients fromtwo unrelated families.CLDN10Bencodes Claudin-10b, an integraltight junction (TJ) membrane-spanning protein expressed in thekidney, skin, and salivary glands. All patients had hypohidrosis,renal loss of NaCl with secondary hyperaldosteronism andhypokalemia, as well as hypolacrymia, ichthyosis, xerostomia,and severe enamel wear. Functional testing revealed that patientshad a decreased NaCl absorption in the thick ascending limb of theloop of Henle and a severely decreased secretion of saliva. Bothmutations resulted in reduced or absent Claudin-10 at the plasmamembrane of epithelial cells.Conclusion:CLDN10mutations cause a dysfunction in TJs inseveral tissues and, subsequently, abnormalities in renal iontransport, ectodermal gland homeostasis, and epidermalintegrity.

Keywords : CLDN10 ectodermal glands multiple epitheliadysfunction paracellular transport tight junctions

Document type :

Journal articles

Domain :

Life Sciences [q-bio]

Complete list of metadatas

https://hal-univ-evry.archives-ouvertes.fr/hal-02173103
Contributor : Olek Maciejak <>
Submitted on : Thursday, July 4, 2019 - 11:39:44 AM
Last modification on : Thursday, October 3, 2019 - 8:16:10 PM

Multiplex epithelium dysfunction due to CLDN10 mutation: the HELIX syndrome

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Multiplex epithelium dysfunction due to CLDN10 mutation: the HELIX syndrome

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