| Added by | informatique.ircm |
|---|---|
| Group name | Informatique |
| Item Type | Journal Article |
| Title | POLR1B and neural crest cell anomalies in Treacher Collins syndrome type 4 |
| Creator | Sanchez et al. |
| Author | Elodie Sanchez |
| Author | Béryl Laplace-Builhé |
| Author | Frédéric Tran Mau-Them |
| Author | Eric Richard |
| Author | Alice Goldenberg |
| Author | Tomi L. Toler |
| Author | Thomas Guignard |
| Author | Vincent Gatinois |
| Author | Marie Vincent |
| Author | Catherine Blanchet |
| Author | Anne Boland |
| Author | Marie Thérèse Bihoreau |
| Author | Robert Olaso |
| Author | Walton Nephi |
| Author | Hermann-Josef Lüdecke |
| Author | Joke B. G. M. Verheij |
| Author | Florence Moreau-Lenoir |
| Author | Françoise Denoyelle |
| Author | Jean-Baptiste Rivière |
| Author | Jean-Louis Laplanche |
| Author | Marcia Willing |
| Author | Guillaume Captier |
| Author | Florence Apparailly |
| Author | Dagmar Wieczorek |
| Author | Corinne Collet |
| Author | Farida Djouad |
| Author | David Geneviève |
| Abstract | PURPOSE: Treacher Collins syndrome (TCS) is a rare autosomal dominant mandibulofacial dysostosis, with a prevalence of 0.2-1/10,000. Features include bilateral and symmetrical malar and mandibular hypoplasia and facial abnormalities due to abnormal neural crest cell (NCC) migration and differentiation. To date, three genes have been identified: TCOF1, POLR1C, and POLR1D. Despite a large number of patients with a molecular diagnosis, some remain without a known genetic anomaly. METHODS: We performed exome sequencing for four individuals with TCS but who were negative for pathogenic variants in the known causative genes. The effect of the pathogenic variants was investigated in zebrafish. RESULTS: We identified three novel pathogenic variants in POLR1B. Knockdown of polr1b in zebrafish induced an abnormal craniofacial phenotype mimicking TCS that was associated with altered ribosomal gene expression, massive p53-associated cellular apoptosis in the neuroepithelium, and reduced number of NCC derivatives. CONCLUSION: Pathogenic variants in the RNA polymerase I subunit POLR1B might induce massive p53-dependent apoptosis in a restricted neuroepithelium area, altering NCC migration and causing cranioskeletal malformations. We identify POLR1B as a new causative gene responsible for a novel TCS syndrome (TCS4) and establish a novel experimental model in zebrafish to study POLR1B-related TCS. |
| Publication | Genetics in Medicine: Official Journal of the American College of Medical Genetics |
| Volume | 22 |
| Issue | 3 |
| Pages | 547-556 |
| Date | Mar 2020 |
| Journal Abbr | Genet. Med. |
| Language | eng |
| DOI | 10.1038/s41436-019-0669-9 |
| ISSN | 1530-0366 |
| Library Catalog | PubMed |
| Extra | PMID: 31649276 PMCID: PMC7056642 |
| Tags | POLR1B, Treacher Collins - Franceschetti |
| Date Added | 2020/05/26 - 12:31:22 |
| Date Modified | 2020/05/26 - 12:31:22 |
| Notes and Attachments | PubMed entry (Attachment) Texte intégral (Attachment) |
Institut de Recherche en Cancérologie de
