Identification of novel mutations in SHH and ZIC2 in a South American (ECLAMC) population with holoprosencephaly.
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.
Orioli
I M
IM
Department of Pediatrics and Genetics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Castilla
E E
EE
Ming
J E
JE
Nazer
J
J
Burle de Aguiar
M J
MJ
Llerena
J C
JC
Muenke
M
M
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*
D053823:Hedgehog Proteins; D009687:Nuclear Proteins; C509239:SHH protein, human; D015534:Trans-Activators; D014157:Transcription Factors; C491812:ZIC2 protein, human; D004247:DNA