title: Holoprosencephaly in a family segregating novel variants in ZIC2 and GLI2.
abstract: Holoprosencephaly (HPE) is the most common malformation of the human forebrain. Typical manifestations in affected patients include a characteristic pattern of structural brain and craniofacial anomalies. HPE may be caused by mutations in over 10 identified genes; the inheritance is traditionally viewed as autosomal dominant with highly variable expressivity and incomplete penetrance. We present the description of a family simultaneously segregating two novel variants in the HPE-associated genes, ZIC2 and GLI2, as well as the results of extensive population-based studies of the variant region in GLI2. This is the first time that multiple HPE-associated variants in these genes have been reported in one family, and raises important questions about how clinicians and researchers should view the inheritance of conditions such as HPE.
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Nilrat
authors.initials: N
authors.lastname: Wannasilp
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Solomon
authors.forename: Nicole
authors.initials: N
authors.lastname: Warren-Mora
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Clegg
authors.forename: Mauricio R
authors.initials: MR
authors.lastname: Delgado
authors.forename: Felicitas
authors.initials: F
authors.lastname: Lacbawan
authors.forename: Ping
authors.initials: P
authors.lastname: Hu
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Winder
authors.forename: Erich
authors.initials: E
authors.lastname: Roessler
authors.forename: Maximilian
authors.initials: M
authors.lastname: Muenke
mesh_terms: D000595:Amino Acid Sequence; D002648:Child; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D016142:Holoprosencephaly / Q000000981:diagnostic imaging / Q000235:genetics*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D011859:Radiography; D014157:Transcription Factors / Q000235:genetics*; D000075746:Zinc Finger Protein Gli2
chemical_list: C082593:GLI2 protein, human; D051741:Kruppel-Like Transcription Factors; D009687:Nuclear Proteins; D014157:Transcription Factors; C491812:ZIC2 protein, human; D000075746:Zinc Finger Protein Gli2