title: Identification of novel mutations in SHH and ZIC2 in a South American (ECLAMC) population with holoprosencephaly.
abstract: Holoprosencephaly (HPE) is genetically heterogeneous with four genes, SIX3, SHH, TGIF, and ZIC2 that have been identified to date and that are altered in 12% of patients. To analyze this prevalence in a South American population-based sample (57 HPE cases in 244,511 live and still births or 1 in 4300), we performed a mutational study of these genes in 30 unrelated children (26 newborns and 4 non-newborns) with HPE being ascertained by ECLAMC (Latin American Collaborative Study of Congenital Malformations). We identified three novel mutations: two were missense mutations of the SHH gene (Cys183-->Phe; His140-->Pro); the third mutation was a 2-bp deletion in the zinc-finger region of the ZIC2 gene. These molecular results explained 8% (2/26 newborn samples) of the HPE cases in this South American population-based sample, a proportion similar to our previously published data from a collection of cases.
authors.affiliation: Department of Pediatrics and Genetics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: I M
authors.initials: IM
authors.lastname: Orioli
authors.forename: E E
authors.initials: EE
authors.lastname: Castilla
authors.forename: J E
authors.initials: JE
authors.lastname: Ming
authors.forename: J
authors.initials: J
authors.lastname: Nazer
authors.forename: M J
authors.initials: MJ
authors.lastname: Burle de Aguiar
authors.forename: J C
authors.initials: JC
authors.lastname: Llerena
authors.forename: M
authors.initials: M
authors.lastname: Muenke
mesh_terms: D001483:Base Sequence; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005313:Fetal Death / Q000235:genetics; D005828:Genetics, Population; D053823:Hedgehog Proteins; D016142:Holoprosencephaly / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D009687:Nuclear Proteins; D017384:Sequence Deletion; D013020:South America / Q000453:epidemiology; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D053823:Hedgehog Proteins; D009687:Nuclear Proteins; C509239:SHH protein, human; D015534:Trans-Activators; D014157:Transcription Factors; C491812:ZIC2 protein, human; D004247:DNA