Curation RCPS EIF4A3

Gene EIF4A3

Disease RCPS

Inheritance AR

Score

9 + 6 = 15 / 18

Genetic + experimental = total

Classification

Definitive

Refuted

Moderate

Definitive

Last Updated 06/02/2025

Pubs Reviewed 3

Publication Span 4.24 years

Publication Interval 4.24 years

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.

All criTRia Curations Locus Page

Genetic evidence

Total: 9

Per page

Category	Type	Citation	Score	Details
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

Per page

Category	Type	Citation	Score	Details
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.

Maximum score caps apply at evidence type, category, and supercategory levels, so section totals may be lower than the raw sum of row scores.