title: Molecular characterization of breakpoints in patients with holoprosencephaly and definition of the HPE2 critical region 2p21.
abstract: Holoprosencephaly (HPE) is a common developmental defect involving the brain and face in humans. Cytogenetic deletions in patients with HPE have localized one of the HPE genes (HPE2) to the chromosomal region 2p21. Here we report the molecular genetic characterization of nine HPE patients with cytogenetic deletions or translocations involving 2p21. We have determined the parental origin of the deleted chromosomes and defined the HPE2 critical region between D2S119 and D2S88/D2S391. As a first step towards cloning the HPE2 gene which is crucial for normal brain development we have constructed a YAC contig which spans the smallest region of deletion overlap. Several of these YACs could be identified which span three different 2p21 breakpoints in HPE patients. These YACs narrow the HPE2 critical region to less than 1 Mb and are now being further analyzed to identify the gene causing holoprosencephaly on chromosome 2.
authors.affiliation: Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia 19104-4399, USA.
authors.forename: U
authors.initials: U
authors.lastname: Schell
authors.forename: J
authors.initials: J
authors.lastname: Wienberg
authors.forename: A
authors.initials: A
authors.lastname: Köhler
authors.forename: P
authors.initials: P
authors.lastname: Bray-Ward
authors.forename: D E
authors.initials: DE
authors.lastname: Ward
authors.forename: W G
authors.initials: WG
authors.lastname: Wilson
authors.forename: W P
authors.initials: WP
authors.lastname: Allen
authors.forename: R R
authors.initials: RR
authors.lastname: Lebel
authors.forename: J R
authors.initials: JR
authors.lastname: Sawyer
authors.forename: P L
authors.initials: PL
authors.lastname: Campbell
authors.forename: D J
authors.initials: DJ
authors.lastname: Aughton
authors.forename: H H
authors.initials: HH
authors.lastname: Punnett
authors.forename: E J
authors.initials: EJ
authors.lastname: Lammer
authors.forename: F T
authors.initials: FT
authors.lastname: Kao
authors.forename: D C
authors.initials: DC
authors.lastname: Ward
authors.forename: M
authors.initials: M
authors.lastname: Muenke
mesh_terms: D001483:Base Sequence; D002874:Chromosome Mapping; D018244:Chromosomes, Artificial, Yeast; D002889:Chromosomes, Human, Pair 2; D003001:Cloning, Molecular; D017931:DNA Primers; D015342:DNA Probes; D005260:Female; D017353:Gene Deletion; D016142:Holoprosencephaly / Q000235:genetics*; D006801:Humans; D006822:Hybrid Cells; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D014178:Translocation, Genetic
chemical_list: D017931:DNA Primers; D015342:DNA Probes