DISORGANIZATION IN MICE AND HUMANS AND ITS RELATION TO SPORADIC BIRTH-DEFECTS

Disorganization (Ds) is a mouse mutant best known for producing an exc eptional variety of unusual developmental anomalies, such as mirror-li mb duplications and hamartomatous skin papillae, So great is the range of malformations that no two affected mice are identical, Several pat ients with a similar variety of exceptional anomalies have been report ed, raising the possibility of the existence of a human homologue of D s, However, although these human cases represent the most striking fin dings seen in Ds mice, they do not represent the full range of defects , Most affected mice have only a single malformation, and most of thes e malformations are similar to both common (neural tube defects, orofa cial clefting, gastroschisis, limb reductions) and rare (anophthalmia, duplicated rectum) human birth defects, It is therefore possible that the full spectrum of the human homologue of Ds includes not only pati ents with the unusual combination of anomalies but also common sporadi c birth defects, We suggest that the low penetrance (similar to 0-30%) and highly variable expression of Ds make it a paradigm for understan ding the genetic basis for many seemingly sporadic birth defects. (C) 1997 Wiley-Liss, Inc.