RCPS_EIF4A3
- Gene
- EIF4A3
- Disease
- RCPS
- Inheritance
- AR
- Classification
- Definitive
- Total Score
- 15
- Publications Reviewed
- 3
- Publication Span
- 4.24 years
- Last Updated
- 06/02/2025
- Curator(s)
- Laurel Hiatt
Description
Richieri-Costa-Pereira syndrome (RCPS) is an autosomal recessive acrofacial dysostosis caused primarily by biallelic EIF4A3 5' UTR repeat expansions, most commonly 15-16 repeats compared with 3-12 repeats in controls, with additional pathogenic compound heterozygosity involving a 14-repeat allele and EIF4A3 missense variant. The locus-disease relationship is supported by affected families/probands with biallelic EIF4A3 variants, linkage and segregation at 17q25.3, reduced EIF4A3 expression and neural crest/osteochondrogenic defects in patient-derived cells, and zebrafish and mouse models of EIF4A3 deficiency that reproduce craniofacial developmental abnormalities relevant to RCPS.
Genetic evidence
Total: 9
| Singular Evidence | Probands | PMID:29112243 | 6 | Seven affected individuals from six families had RCPS clinical features and biallelic EIF4A3 variants involving 14-, 15-, or 16-repeat 5' UTR expansion alleles and/or c.809A>G in trans; the cohort included mild and severe presentations and expanded the phenotypic/genotypic spectrum. |
| Collective Evidence | Segregation | PMID:24360810 | 3 | Linkage and segregation in 20 affected individuals from 17 families refined the RCPS locus to 17q25.3 and showed significant linkage at rs2289534 (maximum LOD 9.533); expanded EIF4A3 5' UTR alleles segregated with autosomal-recessive disease in tested families. |
Experimental evidence
Total: 6
| Functional Alteration | Patient cells | PMID:28334780 | 2 | RCPS patient-derived iPSCs were differentiated into iNCCs and nMSCs; RCPS iNCCs showed reduced EIF4A3 mRNA/protein and decreased wound-healing migration, while nMSCs showed altered chondrogenic markers and premature osteogenic differentiation. |
| Models | Non-human model organism | PMID:28334780 | 3 | Gene-level, not repeat-allele-specific: conditional Eif4a3 haploinsufficient mouse models, including NCC-specific Wnt1-Cre;Eif4a3lx/+ embryos, showed RCPS-relevant craniofacial defects including impaired mandibular development, micrognathia, reduced Meckel's cartilage, premature clavicle ossification, and mandibular hypoplasia. |
| Models | Non-human model organism | PMID:24360810 | 2 | Gene-level, not repeat-allele-specific: zebrafish eif4a3 morpholino knockdown caused craniofacial cartilage and bone underdevelopment, lower-jaw clefting, and underdeveloped pharyngeal arches; most abnormalities were rescued by eif4a3-EGFP mRNA. |
Note: Maximum score caps apply at evidence type, category, and supercategory levels, so section totals may be lower than the raw sum of row scores.