title: Gene encoding a new RING-B-box-Coiled-coil protein is mutated in mulibrey nanism.
abstract: Mulibrey nanism (for muscle-liver-brain-eye nanism, MUL; MIM 253250) is an autosomal recessive disorder that involves several tissues of mesodermal origin, implying a defect in a highly pleiotropic gene. Characteristic features include severe growth failure of prenatal onset and constrictive pericardium with consequent hepatomegaly. In addition, muscle hypotonia, J-shaped sella turcica, yellowish dots in the ocular fundi, typical dysmorphic features and hypoplasia of various endocrine glands causing hormonal deficiency are common. About 4% of MUL patients develop Wilms' tumour. MUL is enriched in the Finnish population, but is rare elsewhere. We previously assigned MUL to chromosome 17q22-q23 and constructed a physical contig over the critical MUL region. The region has now been further refined by haplotype analysis and new positional candidate genes have been localized. We identified a gene with four independent MUL-associated mutations that all cause a frameshift and predict a truncated protein. MUL is ubiquitously expressed and encodes a new member of the RING-B-box-Coiled-coil (RBCC) family of zinc-finger proteins, whose members are involved in diverse cellular functions such as developmental patterning and oncogenesis.
authors.affiliation: Folkhälsan Institute of Genetics, Helsinki, Finland. Kristiina.Avela@helsinki.fi
authors.forename: K
authors.initials: K
authors.lastname: Avela
authors.forename: M
authors.initials: M
authors.lastname: Lipsanen-Nyman
authors.forename: N
authors.initials: N
authors.lastname: Idänheimo
authors.forename: E
authors.initials: E
authors.lastname: Seemanová
authors.forename: S
authors.initials: S
authors.lastname: Rosengren
authors.forename: T P
authors.initials: TP
authors.lastname: Mäkelä
authors.forename: J
authors.initials: J
authors.lastname: Perheentupa
authors.forename: A D
authors.initials: AD
authors.lastname: Chapelle
authors.forename: A E
authors.initials: AE
authors.lastname: Lehesjoki
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D018388:Codon, Terminator; D018076:DNA, Complementary; D004392:Dwarfism / Q000235:genetics*; D016368:Frameshift Mutation; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics*; D051381:Rats; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases; D016335:Zinc Fingers
chemical_list: D018388:Codon, Terminator; D018076:DNA, Complementary; D009687:Nuclear Proteins; D000070584:Tripartite Motif Proteins; C411745:TRIM37 protein, human; D044767:Ubiquitin-Protein Ligases