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Title: Digenic inheritance of mutations in EPHA2 and SLC26A4 in Pendred syndrome
Authors: Li, Mengnan
Nishio, Shin-ya
Naruse, Chie  kyouindb  KAKEN_id
Riddell, Meghan
Sapski, Sabrina
Katsuno, Tatsuya
Hikita, Takao
Mizapourshafiyi, Fatemeh
Smith, Fiona M.
Cooper, Leanne T.
Lee, Min Goo
Asano, Masahide  kyouindb  KAKEN_id
Boettger, Thomas
Krueger, Marcus
Wietelmann, Astrid
Graumann, Johannes
Day, Bryan W.
Boyd, Andrew W.
Offermanns, Stefan
Kitajiri, Shin-ichiro
Usami, Shin-ichi
Nakayama, Masanori
Author's alias: 西尾, 信哉
成瀬, 智恵
勝野, 達也
匹田, 貴夫
浅野, 雅秀
北尻, 真一郎
宇佐美, 真一
中山, 雅敬
Keywords: Cell polarity
Issue Date: 12-Mar-2020
Publisher: Springer Nature
Journal title: Nature Communications
Volume: 11
Thesis number: 1343
Abstract: Enlarged vestibular aqueduct (EVA) is one of the most commonly identified inner ear malformations in hearing loss patients including Pendred syndrome. While biallelic mutations of the SLC26A4 gene, encoding pendrin, causes non-syndromic hearing loss with EVA or Pendred syndrome, a considerable number of patients appear to carry mono-allelic mutation. This suggests faulty pendrin regulatory machinery results in hearing loss. Here we identify EPHA2 as another causative gene of Pendred syndrome with SLC26A4. EphA2 forms a protein complex with pendrin controlling pendrin localization, which is disrupted in some pathogenic forms of pendrin. Moreover, point mutations leading to amino acid substitution in the EPHA2 gene are identified from patients bearing mono-allelic mutation of SLC26A4. Ephrin-B2 binds to EphA2 triggering internalization with pendrin inducing EphA2 autophosphorylation weakly. The identified EphA2 mutants attenuate ephrin-B2- but not ephrin-A1-induced EphA2 internalization with pendrin. Our results uncover an unexpected role of the Eph/ephrin system in epithelial function.
Rights: © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit
DOI(Published Version): 10.1038/s41467-020-15198-9
PubMed ID: 32165640
Appears in Collections:Journal Articles

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