Molecular characterization of breakpoints in patients with holoprosencephaly and definition of the HPE2 critical region 2p21

Holoprosencephaly (HPE) is a common developmental defect involving thebrain and face in humans. Cytogenetic deletions in patients with HPE havelocalized one of the HPE genes (HPE2) to the chromosomal region 2p21. Herewe report the molecular genetic characterization of nine HPE patients withcytogenetic deletions or translocations involving 2p21. We have determinedthe parental origin of the deleted chromosomes and defined the HPE2critical region between D2S119 and D2S88/D2S391. As a first step towardscloning the HPE2 gene which is crucial for normal brain development we haveconstructed a YAC contig which spans the smallest region of deletionoverlap. Several of these YACs could be identified which span threedifferent 2p21 breakpoints in HPE patients. These YACs narrow the HPE2critical region to less than 1 Mb and are now being further analyzed toidentify the gene causing holoprosencephaly on chromosome 2.