title: Structure of the human Lanosterol synthase gene and its analysis as a candidate for holoprosencephaly (HPE1).
abstract: Holoprosencephaly (HPE) is the most common birth defect of the brain in humans. It involves various degrees of incomplete separation of the cerebrum into distinct left and right halves, and it is frequently accompanied by craniofacial anomalies. The HPE1 locus in human chromosome 21q22.3 is one of a dozen putative genetic loci implicated in causing HPE. Here, we report the complete gene structure of the human lanosterol synthase (LS) gene, which is located in this interval, and present its mutational analysis in HPE patients. We considered LS an excellent candidate HPE gene because of the requirement for cholesterol modification of the Sonic Hedgehog protein for the correct patterning activity of this HPE-associated protein. Despite extensive pedigree analysis of numerous polymorphisms, as well as complementation studies in yeast on one of the missense mutations, we find no evidence that the LS gene is in fact HPE1, implicating another gene located in this chromosomal region in HPE pathogenesis.
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda MD 20892-1852, USA.
authors.forename: E
authors.initials: E
authors.lastname: Roessler
authors.forename: L
authors.initials: L
authors.lastname: Mittaz
authors.forename: Y
authors.initials: Y
authors.lastname: Du
authors.forename: H S
authors.initials: HS
authors.lastname: Scott
authors.forename: J
authors.initials: J
authors.lastname: Chang
authors.forename: C
authors.initials: C
authors.lastname: Rossier
authors.forename: M
authors.initials: M
authors.lastname: Guipponi
authors.forename: S P
authors.initials: SP
authors.lastname: Matsuda
authors.forename: M
authors.initials: M
authors.lastname: Muenke
authors.forename: S E
authors.initials: SE
authors.lastname: Antonarakis
mesh_terms: D001483:Base Sequence; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D005091:Exons; D005260:Female; D005816:Genetic Complementation Test; D016142:Holoprosencephaly / Q000201:enzymology* / Q000235:genetics*; D006801:Humans; D019751:Intramolecular Transferases / Q000235:genetics*; D007438:Introns; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012441:Saccharomyces cerevisiae / Q000235:genetics
chemical_list: D017931:DNA Primers; D018076:DNA, Complementary; D019751:Intramolecular Transferases; C021924:lanosterol synthase