Identification of novel mutations in SHH and ZIC2 in a South American (ECLAMC) population with holoprosencephaly

Hum Genet. 2001 Jul;109(1):1-6. doi: 10.1007/s004390100537.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • DNA / genetics
  • DNA Mutational Analysis
  • Female
  • Fetal Death / genetics
  • Genetics, Population
  • Hedgehog Proteins
  • Holoprosencephaly / epidemiology
  • Holoprosencephaly / genetics*
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Mutation*
  • Mutation, Missense
  • Nuclear Proteins
  • Sequence Deletion
  • South America / epidemiology
  • Trans-Activators / genetics*
  • Transcription Factors / genetics*

Substances

  • Hedgehog Proteins
  • Nuclear Proteins
  • SHH protein, human
  • Trans-Activators
  • Transcription Factors
  • ZIC2 protein, human
  • DNA