Interstitial duplication of the short arm of chromosome 1 in a newborn with congenital heart disease and multiple malformations

Interstitial duplications of chromosomes Ip are rare, with only 14 cases pr eviously reported in the literature, and those have not revealed a unique s yndrome. The phenotypes include multiple congenital abnormalities and both intra- and extra-uterine growth retardation, in general, the patients do po orly and do not survive beyond the age of several months. We report a newbo rn male with karyotype 46, W, inv dup(1)(qter --> p34.3::p34.3 --> p32.3::3 4.3 --> pter) with multiple congenital abnormalities including congenital h eart disease and co-existing portal and pulmonary hypertension. The chromos ome 1 origin of the extra material was confirmed with fluorescent in situ h ybridization (FISH). Review of the GDB [Human Genome Database, 1990] reveal s that the duplicated region includes the locus EDN2 that encodes endotheli n-l, a potent vasoconstrictor, making genetic overdosage of this protein a likely etiology of the pulmonary hypertension The diffuse abnormalities sho w effects in multiple cell lines and suggest that this region of chromosome Ip could be involved in determining cell migration and/or differentiation during organogenesis, (C) 2001 Wiley-Liss, Inc.