Journal article
Multiplex epithelium dysfunction due to CLDN10 mutation: the HELIX syndrome
Genetics in medicine, Vol.20(2), pp.190-201
02/2018
DOI: 10.1038/gim.2017.71
PMID: 28771254
Abstract
Purpose
We aimed to identify the genetic cause to a clinical syndrome encompassing hypohidrosis, electrolyte imbalance, lacrimal gland dysfunction, ichthyosis, and xerostomia (HELIX syndrome), and to comprehensively delineate the phenotype.
Methods
We performed homozygosity mapping, whole-genome sequencing, gene sequencing, expression studies, functional tests, protein bioinformatics, and histological characterization in two unrelated families with HELIX syndrome.
Results
We identified biallelic missense mutations (c.386C>T, p.S131L and c.2T>C, p.M1T) in CLDN10B in six patients from two unrelated families. CLDN10B encodes Claudin-10b, an integral tight junction (TJ) membrane-spanning protein expressed in the kidney, skin, and salivary glands. All patients had hypohidrosis, renal loss of NaCl with secondary hyperaldosteronism and hypokalemia, as well as hypolacrymia, ichthyosis, xerostomia, and severe enamel wear. Functional testing revealed that patients had a decreased NaCl absorption in the thick ascending limb of the loop of Henle and a severely decreased secretion of saliva. Both mutations resulted in reduced or absent Claudin-10 at the plasma membrane of epithelial cells.
Conclusion
CLDN10 mutations cause a dysfunction in TJs in several tissues and, subsequently, abnormalities in renal ion transport, ectodermal gland homeostasis, and epidermal integrity.
Details
- Title: Subtitle
- Multiplex epithelium dysfunction due to CLDN10 mutation: the HELIX syndrome
- Creators
- Smail Hadj-Rabia - Université Paris CitéGaelle Brideau - Marie CurieYasser Al-Sarraj - Qatar Biomedical Research InstituteRachid C Maroun - Université d'Évry Val-d'EssonneMarie-Lucile Figueres - Marie CurieStéphanie Leclerc-Mercier - Hôpital Necker-Enfants MaladesEric Olinger - University of ZurichStéphanie Baron - Marie CurieCatherine Chaussain - Assistance Publique – Hôpitaux de ParisDominique Nochy - Hôpital Européen Georges-PompidouRowaida Z Taha - Qatar Biomedical Research Institute, Hamad Ben Khalifa University, Doha, QatarBertrand Knebelmann - Hôpital Necker-Enfants MaladesVandana JoshiPatrick A Curmi - Université d'Évry Val-d'EssonneMarios Kambouris - Hamad bin Khalifa UniversityRosa Vargas-Poussou - Marie CurieChristine Bodemer - Université Paris CitéOlivier Devuyst - University of ZurichPascal Houillier - Marie CurieHatem El-Shanti - University of Jordan
- Resource Type
- Journal article
- Publication Details
- Genetics in medicine, Vol.20(2), pp.190-201
- DOI
- 10.1038/gim.2017.71
- PMID
- 28771254
- ISSN
- 1098-3600
- eISSN
- 1530-0366
- Language
- English
- Date published
- 02/2018
- Academic Unit
- Stead Family Department of Pediatrics; Medical Genetics and Genomics
- Record Identifier
- 9984353889402771
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