Mutational analysis of the Sonic Hedgehog gene in 220 newborns with oral clefts in a South American (ECLAMC) population

Authors

  • Iêda M. Orioli,

    1. Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
    2. Latin American Collaborative Study of Congenital Malformations (ECLAMC) at Department of Genetics, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil
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  • Alexandre R. Vieira,

    1. Latin American Collaborative Study of Congenital Malformations (ECLAMC) at Department of Genetics, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil
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  • Eduardo E. Castilla,

    1. ECLAMC at Department of Genetics, Instituto Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
    2. ECLAMC at Cemic, Buenos Aires, Argentina
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  • Jeffrey E. Ming,

    1. Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
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  • Maximilian Muenke

    Corresponding author
    1. Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
    2. Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland
    • Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, 10 Center Drive, MSC 1852, Building 10, 10C101, Bethesda, MD 20892-1852.

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  • This article was prepared by a group consisting of both United State Government employees and non-United States Government employees, and as such is subject to 117 U.S.C. Sec. 105.

Abstract

Oral clefts generally have a multifactorial etiology. A number of genes contribute to the formation of the face and palate. Cleft lip and/or palate can occur in pedigrees with autosomal dominant holoprosencephaly due to mutations in Sonic Hedgehog (SHH). In addition, animal models have shown that SHH is involved in face development. We thus examined the human SHH gene in 220 newborn infants with nonsyndromic oral clefts registered by the Estudio Colaborativo Latinoamericano de Malformaciones Congenitas: ECLAMC (Latin American Collaborative Study of Congenital Malformations). We found 15 variant bands in 13 patients with oral clefts, representing five different base changes, all of which were found by sequencing to represent silent polymorphisms. Four occurred in introns. The alteration occurring in an exon, Ser190Ser, may create a consensus sequence for the 3′splice site 6 bp downstream of the original consensus sequence. Thus, we did not identify any clearly disease-causing mutation in SHH in these patients, and conclude that SHH mutations are not a frequent cause of isolated oral clefts in humans. Published 2002 Wiley-Liss, Inc.

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