Academic Journal
The interleukin-11 receptor variant p.W307R results in craniosynostosis in humans
| Title: | The interleukin-11 receptor variant p.W307R results in craniosynostosis in humans |
|---|---|
| Authors: | Ilyas Ahmad, Juliane Lokau, Birte Kespohl, Naveed Altaf Malik, Shahid Mahmood Baig, Roland Hartig, Daniel Behme, Roland Schwab, Janine Altmüller, Muhammad Jameel, Sören Mucha, Holger Thiele, Muhammad Tariq, Peter Nürnberg, Jeanette Erdmann, Christoph Garbers |
| Source: | Scientific Reports, Vol 13, Iss 1, Pp 1-14 (2023) |
| Publisher Information: | Nature Portfolio, 2023. |
| Publication Year: | 2023 |
| Collection: | LCC:Medicine LCC:Science |
| Subject Terms: | Medicine, Science |
| More Details: | Abstract Craniosynostosis is characterized by the premature fusion and ossification of one or more of the sutures of the calvaria, often resulting in abnormal features of the face and the skull. In cases in which growth of the brain supersedes available space within the skull, developmental delay or cognitive impairment can occur. A complex interplay of different cell types and multiple signaling pathways are required for correct craniofacial development. In this study, we report on two siblings with craniosynostosis and a homozygous missense pathogenic variant within the IL11RA gene (c.919 T > C; p.W307R). The patients present with craniosynostosis, exophthalmos, delayed tooth eruption, mild platybasia, and a basilar invagination. The p.W307R variant is located within the arginine-tryptophan-zipper within the D3 domain of the IL-11R, a structural element known to be important for the stability of the cytokine receptor. Expression of IL-11R-W307R in cells shows impaired maturation of the IL-11R, no transport to the cell surface and intracellular retention. Accordingly, cells stably expressing IL-11R-W307R do not respond when stimulated with IL-11, arguing for a loss-of-function mutation. In summary, the IL-11R-W307R variant, reported here for the first time to our knowledge, is most likely the causative variant underlying craniosynostosis in these patients. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2045-2322 |
| Relation: | https://doaj.org/toc/2045-2322 |
| DOI: | 10.1038/s41598-023-39466-y |
| Access URL: | https://doaj.org/article/37abbe8ef1aa4c21a5485f639564dcf7 |
| Accession Number: | edsdoj.37abbe8ef1aa4c21a5485f639564dcf7 |
| Database: | Directory of Open Access Journals |
| Full text is not displayed to guests. | Login for full access. |
| ISSN: | 20452322 |
|---|---|
| DOI: | 10.1038/s41598-023-39466-y |
| Published in: | Scientific Reports |
| Language: | English |