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(1). Characteristic features include severe growth failure of prenatal onset and constrictive pericardium with consequent hepatomegaly(1-3).
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 (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 physical contig over the critical MUL region(6,7).
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 RINC-B-box-Coiled-coil (RBCC) family of zinc-finger proteins(8-10), whose members are involved in diverse cellular functions such as developmental patterning and oncogenesis.