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| Author(s): |
Francine Pinheiro Favaro
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | Bauru. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Odontologia de Bauru (FOB/SDB) |
| Defense date: | 2013-10-08 |
| Examining board members: |
Daniela Gamba Garib Carreira;
Débora Romeo Bertola;
Maria Rita dos Santos e Passos Bueno;
Roseli Maria Zechi Ceide;
Antonio Richieri da Costa
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| Advisor: | Maria Leine Guion de Almeida |
| Abstract | |
Introduction: Richieri-Costa-Pereira syndrome (RCPS; MIM#268305) is an autosomal recessive acrofacial dysostosis characterized by mandibular median cleft associated with other craniofacial and limb defects. Purpose: Map the gene that causes the SRCP. Methods and Results: We mapped the disease gene to a 128.5kb region on chromosome 17q25.3 through identity-by-descent analysis in 22 genealogies. Sequencing strategies identified an expansion of a complex region with several repeats of 18 or 20-nucleotide motifs in the 5 untranslated region (5´UTR) of EIF4A3, which contained from 15 or 16 repeats in the affected patients and from 3 to 12 repeats in 520 healthy individuals. EIF4A3 transcriptional levels were markedly reduced in white blood cells of a RCPS patient as compared to controls. Furthermore, modeling of the ortholog eif4a3 in zebrafish lead to underdevelopment of several cartilage and bone craniofacial structures derived from the 1st to 5th pharyngeal arches, in agreement with the craniofacial alterations of RCPS. Conclusion: These studies thus confirm that RCPS is caused by deficiency of EIF4A3, and assign EIF4A3 for the first time as essential for mandibular and also for larynx and limb morphogenesis, important structures impaired in RCPS. (AU) | |
| FAPESP's process: | 10/17712-5 - Genic locus investigation in families with the Richieri-Costa-Pereira Syndrome |
| Grantee: | Francine Pinheiro Favaro |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |