Wolf-Hirschhorn syndrome (WHS) is a multiple malformation syndrome characterized by mental and developmental defects resulting from the absence of a segment of one chromosome 4 short arm (4p16.3). Recently, Pitt-Rogers-Danks syndrome (PRDS), which is also due to a deletion of chromosome 4p16.3, has been shown to be allelic to WHS. Due to the complex and variable expression of these disorders, it is thought that WHS/PRDS results from a segmental aneusomy of 4p resulting in haploinsufficieny of an undefined number of genes that contribute to the phenotype. In an effort to identify genes that contribute to human development and whose absence may contribute to the phenotype associated with these syndromes, we have generated a transcript map of the 165-kb critical region and have identified a number of potential genes. One of these genes, WHSC2, which was identified with the IMAGE cDNA clone 53283, has been characterized. Sequence analysis defined an open reading frame of 1584 bp (528 amino acids), and transcript analysis detected a 2.4-kb transcript in all fetal and adult tissues tested. In parallel, the mouse homologue was isolated and characterized. Mouse sequence analysis and the pattern of expression are consistent with the clone being the murine equivalent of the human WHSC2 gene (designated Whsc2h). The data from sequence and transcript analysis of this new human gene in combination with the lack of significant similarity to proteins of known function imply that it represents a novel gene. Most importantly, its location within the WHSCR suggests that this gene may play a role in the phenotype of the Wolf-Hirschhorn/Pitt-Rogers-Danks syndrome.
Copyright 1999 Academic Press.