Holoprosencephaly and holoprosencephaly-like phenotype and GAS1 DNA sequence changes: Report of four Brazilian patients

Authors

  • Lucilene Arilho Ribeiro,

    1. Molecular Genetics Laboratory and Clinical Genetic Service, Hospital for Rehabilitation of Craniofacial Anomalies, USP, Bauru, SP, Brazil
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  • Rodrigo Gonçalves Quiezi,

    1. Molecular Genetics Laboratory and Clinical Genetic Service, Hospital for Rehabilitation of Craniofacial Anomalies, USP, Bauru, SP, Brazil
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  • Adriana Nascimento,

    1. Molecular Genetics Laboratory and Clinical Genetic Service, Hospital for Rehabilitation of Craniofacial Anomalies, USP, Bauru, SP, Brazil
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  • Claudia Pereira Bertolacini,

    1. Molecular Genetics Laboratory and Clinical Genetic Service, Hospital for Rehabilitation of Craniofacial Anomalies, USP, Bauru, SP, Brazil
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  • Antonio Richieri-Costa

    Corresponding author
    1. Molecular Genetics Laboratory and Clinical Genetic Service, Hospital for Rehabilitation of Craniofacial Anomalies, USP, Bauru, SP, Brazil
    • Hospital de Reabilitação de Anomalias Craniofaciais, USP/Bauru, Rua Sílvio Marchione, 3-20, Bauru, SP, Brazil.
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  • How to cite this article: Ribeiro LA, Quiezi RG, Nascimento A, Bertolacini CP, Richieri-Costa A. 2010. Holoprosencephaly and holoprosencephaly-like phenotype and GAS1 DNA sequence changes: Report of four Brazilian patients. Am J Med Genet Part A 152A:1688–1694.

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. © 2010 Wiley-Liss, Inc.

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