Previously undescribed nonsense mutation in SHH caused autosomal dominant holoprosencephaly with wide intrafamilial variability

Monica Marini, Roberto Cusano, Pierangela De Biasio, Francesco Caroli, Margherita Lerone, Margherita Silengo, Roberto Ravazzolo, Marco Seri, Gianni Camera

Research output: Contribution to journalArticle

Abstract

Holoprosencephaly (HPE) is the most common developmental defect of the forebrain and midface in humans, with a frequency of 1/16,000 live births. Different genes are implicated in the pathogenesis of HPE; these include SHH, ZIC2, SIX3, TGIF, and human DKK1. We describe here a family with recurrence of autosomal dominant HPE in different members showing a wide clinical variability. The mother presents a single central maxillary incisor and mild hypotelorism as signs of the diseases, while three of her sons were affected by HPE. By direct sequencing and restriction analysis of exon 2 of the SHH gene, we have identified a previously undescribed nonsense mutation at codon 128 (W128X). The identification of this mutation allowed us to give a prenatal diagnosis in this family and confirms a wide intrafamilial variabilty in the phenotypic spectrum.

Original languageEnglish
Pages (from-to)112-115
Number of pages4
JournalAmerican Journal of Medical Genetics
Volume117 A
Issue number2
Publication statusPublished - Mar 1 2003

Keywords

  • Holoprosencephaly
  • Mutation detection
  • Prenatal diagnosis
  • Single central maxillary incisor
  • Sonic hedgehog gene

ASJC Scopus subject areas

  • Genetics(clinical)

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    Marini, M., Cusano, R., De Biasio, P., Caroli, F., Lerone, M., Silengo, M., Ravazzolo, R., Seri, M., & Camera, G. (2003). Previously undescribed nonsense mutation in SHH caused autosomal dominant holoprosencephaly with wide intrafamilial variability. American Journal of Medical Genetics, 117 A(2), 112-115.