Balanced translocation 12/13 and situs abnormalities: Homology of early pattern formation in man and lower organisms?

Abstract

Studies in “lower” organisms have identified a set of homologous sequences expressed in oocytes and early embryos that is critical for pattern formation. Mutations in such genes may exhibit maternal effect—they cause abnormalities in the fetus only when present in the mother. We report on a mother and child with identical, apparently balanced translocations having the breakpoints 12q13.1 and 13p13. The fetus had multiple anomalies including bilateral trilobar lungs, complex heart defect, malrotation of the gut, and asplenia, while the mother was entirely normal. Several hypotheses are advanced to explain this variable expression including transection of a gene with maternal effect—lateral asymmetry in the fetus is influenced by the maternal genotype. This explanation would account for the higher transmission of congenital heart disease to offspring by affected females noted in several studies. The human counterparts of 2 loci (int‐1 and HOX 3) involved in Drosophila early pattern formation are located near the translocation breakpoint 12q13.1. If one of these genes is responsible for situs abnormality, then universality of positional code (but not of embryologic mechanism) is suggested for higher metazoans.