Tj. Wright et al., Comparative analysis of a novel gene from the Wolf-Hirschhorn/Pitt-Rogers-Danks syndrome critical region, GENOMICS, 59(2), 1999, pp. 203-212
Wolf-Hirschhorn syndrome (WHS) is a multiple malformation syndrome characte
rized by mental and developmental defects resulting from the absence of a s
egment 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 a
neusomy of 4p resulting in haploinsufficieny of an undefined number of gene
s that contribute to the phenotype. In an effort to identify genes that con
tribute to human development and whose absence may contribute to the phenot
ype 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 fr
ame 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 h
omologue was isolated and characterized. Mouse sequence analysis and the pa
ttern of expression are consistent with the clone being the murine equivale
nt 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 represen
ts a novel gene. Most importantly, its location within the WHSCR suggests t
hat this gene may play a role in the phenotype of the Wolf-Hirschhorn/Pitt-
Rogers-Danks syndrome. (C) 1999 Academic Press.