Gene encoding a new RING-B-box-Coiled-coil protein is mutated in mulibrey nanism

Mulibrey nanism (for muscle-liver-brain-eye nanism, MUL; MIM 253250) is an autosomal recessive disorder that involves several tissues of mesodermal or igin, implying a defect in a highly pleiotropic gene(1). Characteristic fea tures include severe growth failure of prenatal onset and constrictive peri cardium with consequent hepatomegaly(1-3). In addition, muscle hypotonia, J -shaped sella turcica, yellowish dots in the ocular fundi, typical dysmorph ic features and hypoplasia of various endocrine glands causing hormonal def iciency are (1-3). About 4% of RAUL patients develop Wilms' common tumour(2 ,4,5). MUL is enriched in the Finnish population, but is rare elsewhere(1-3 ). We previously assigned MUL to chromosome 17q22-q23 and constructed a phy sical contig over the critical MUL region(6,7). The region has now been fur ther refined by haplotype analysis and new positional candidate genes have been localized. We identified a gene with four independent MUL-associated m utations that all cause a frameshift and predict a truncated protein. MUL i s ubiquitously expressed and encodes a new member of the RINC-B-box-Coiled- coil (RBCC) family of zinc-finger proteins(8-10), whose members are involve d in diverse cellular functions such as developmental patterning and oncoge nesis.