biostudies-literatureMarques FNational Institute of Arthritis and Musculoskeletal and Skin DiseasesJoseph Drown FoundationMarch of Dimes FoundationNIAMS NIH HHSNational Institute of General Medical SciencesCAPESNIGMS NIH HHSe1006307https://www.ebi.ac.uk/biostudies/studies/S-EPMC5021280biostudies-literatureUnknown12(9)The acrofacial dysostoses (AFD) are a genetically heterogeneous group of inherited disorders with craniofacial and limb abnormalities. Rodriguez syndrome is a severe, usually perinatal lethal AFD, characterized by severe retrognathia, oligodactyly and lower limb abnormalities. Rodriguez syndrome has been proposed to be a severe form of Nager syndrome, a non-lethal AFD that results from mutations in SF3B4, a component of the U2 small nuclear ribonucleoprotein particle (U2 snRNP). Furthermore, a case with a phenotype intermediate between Rodriguez and Nager syndromes has been shown to have an SF3B4 mutation. We identified heterozygosity for SF3B4 mutations in Rodriguez syndrome, confirming that the phenotype is a dominant disorder that is allelic with Nager syndrome. The mutations led to redPLoS geneticsAltered mRNA Splicing, Chondrocyte Gene Expression and Abnormal Skeletal Development due to SF3B4 Mutations in Rodriguez Acrofacial Dysostosis.PMC5021280RO1AR066124T32 GM0082435T32GM008243PVE-A120/2013564537/2010R01 AR066124noneR01 AR062651R01AR062651Krakow DPogue RTenney JDuran ICohn DHMartin JMarques FLi BNevarez LfalseAltered mRNA Splicing, Chondrocyte Gene Expression and Abnormal Skeletal Development due to SF3B4 Mutations in Rodriguez Acrofacial Dysostosis.The acrofacial dysostoses (AFD) are a genetically heterogeneous group of inherited disorders with craniofacial and limb abnormalities. Rodriguez syndrome is a severe, usually perinatal lethal AFD, characterized by severe retrognathia, oligodactyly and lower limb abnormalities. Rodriguez syndrome has been proposed to be a severe form of Nager syndrome, a non-lethal AFD that results from mutations in SF3B4, a component of the U2 small nuclear ribonucleoprotein particle (U2 snRNP). Furthermore, a case with a phenotype intermediate between Rodriguez and Nager syndromes has been shown to have an SF3B4 mutation. We identified heterozygosity for SF3B4 mutations in Rodriguez syndrome, confirming that the phenotype is a dominant disorder that is allelic with Nager syndrome. The mutations led to red2016-01-01T00:00:00Z2016 Sep2026-04-08T01:58:05.03Z2019-03-26T22:48:08ZS-EPMC50212802762249410.1371/journal.pgen.1006307