title: Holoprosencephaly and holoprosencephaly-like phenotype and GAS1 DNA sequence changes: Report of four Brazilian patients.
abstract: Holoprosencephaly (HPE) is genetically heterogeneous. Variable phenotypic manifestations within families with normal and affected patients have been attributed to the number and type of HPE gene mutations. Environmental agents may also contribute to the severity as well as the requirement of multiple hits. Clinical expression is extremely variable ranging from minor facial signs to complex craniofacial anomalies such as cyclopia. Main genes involved include SHH, GLI2, PTCH1, TGIF, ZIC2, TDGF1, SIX3; however, several other candidates have been proposed. Recently it was established that the human growth arrest specific gene 1 (GAS1) is a potential locus for several human craniofacial malformations. Here, we report on four Brazilian patients with GAS1 DNA sequence change who presented variable phenotypical manifestations ranging from classic HPE to HPE-like signs. Two patients had single DNA sequence change in the GAS1 gene, while in other two, an additional mutation in the SHH gene was observed. Clinical manifestations presented by these patients suggest that GAS1 could be considered a candidate locus for one of the types of human HPE.
authors.affiliation: Molecular Genetics Laboratory and Clinical Genetic Service, Hospital for Rehabilitation of Craniofacial Anomalies, USP, Bauru, SP, Brazil.
authors.forename: Lucilene Arilho
authors.initials: LA
authors.lastname: Ribeiro
authors.forename: Rodrigo Gonçalves
authors.initials: RG
authors.lastname: Quiezi
authors.forename: Adriana
authors.initials: A
authors.lastname: Nascimento
authors.forename: Claudia Pereira
authors.initials: CP
authors.lastname: Bertolacini
authors.forename: Antonio
authors.initials: A
authors.lastname: Richieri-Costa
mesh_terms: D000328:Adult; D001483:Base Sequence; D001938:Brazil; D018797:Cell Cycle Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D019066:Facies; D005260:Female; D058851:GPI-Linked Proteins; D016142:Holoprosencephaly / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D011247:Pregnancy
chemical_list: D018797:Cell Cycle Proteins; C096192:GAS1 protein, human; D058851:GPI-Linked Proteins; D008565:Membrane Proteins