Skip to Main content Skip to Navigation
Journal articles

Copy number variations and founder effect underlying complete IL-10Rβ deficiency in Portuguese kindreds.

Fabienne Charbit-Henrion 1, 2, 3 Bernadette Bègue 1, 3 Anaïs Sierra 1, 3 Sylvain Hanein 4 Marie-Claude Stolzenberg 5 Zhi Li 6 Sandra Pellegrini 6 Nicolas Garcelon 7 Marc Jeanpierre 8, 9 Bénédicte Neven 10, 5 Isabelle Loge 11 Capucine Picard 8, 12 Jeremie Rosain 12, 13 Jacinta Bustamante 4, 14, 12 Marc Le Lorc'H 15 Benedicte Pigneur 2, 1, 3 Alicia Fernandes 16, 4 Frédéric Rieux-Laucat 5 Jorge Amil Dias 17, 3 Frank Ruemmele 2, 1, 3 Nadine Cerf-Bensussan 1 
Abstract : Mutations in interleukin-10 receptor (IL-10R) genes are one cause of very early-onset inflammatory bowel disease with perianal lesions, which can be cured by hematopoietic stem cell transplantation. Using a functional test, which assesses responsiveness of peripheral monocytes to IL-10, we identified three unrelated Portuguese patients carrying two novel IL-10RB mutations. In the three patients, sequencing of genomic DNA identified the same large deletion of exon 3 which precluded protein expression. This mutation was homozygous in two patients born from consanguineous families and heterozygous in the third patient born from unrelated parents. Microsatellite analysis of the IL10RB genomic region revealed a common haplotype in the three Portuguese families pointing to a founder deletion inherited from a common ancestor 400 years ago. In the third patient, surface expression of IL-10R was normal but signaling in response to IL-10 was impaired. Complementary DNA sequencing and next-generation sequencing of IL10RB locus with custom-made probes revealed a ≈ 6 Kb duplication encompassing the exon 6 which leads to a frameshift mutation and a loss of the TYK2-interacting Box 2 motif. Altogether, we describe two novel copy number variations in IL10RB, one with founder effect and one preserving cell surface expression but abolishing signaling.
Document type :
Journal articles
Complete list of metadata

Cited literature [32 references]  Display  Hide  Download
Contributor : Zhi Li Connect in order to contact the contributor
Submitted on : Monday, March 18, 2019 - 12:49:02 PM
Last modification on : Wednesday, September 28, 2022 - 4:20:11 PM
Long-term archiving on: : Wednesday, June 19, 2019 - 5:21:17 PM


Publication funded by an institution


Distributed under a Creative Commons Attribution 4.0 International License



Fabienne Charbit-Henrion, Bernadette Bègue, Anaïs Sierra, Sylvain Hanein, Marie-Claude Stolzenberg, et al.. Copy number variations and founder effect underlying complete IL-10Rβ deficiency in Portuguese kindreds.. PLoS ONE, Public Library of Science, 2018, 13 (10), pp.e0205826. ⟨10.1371/journal.pone.0205826⟩. ⟨pasteur-02070998⟩



Record views


Files downloads