Previously undescribed nonsense mutation in SHH caused autosomal dominant holoprosencephaly with wide intrafamilial variability
✍ Scribed by Monica Marini; Roberto Cusano; Pierangela De Biasio; Francesco Caroli; Margherita Lerone; Margherita Silengo; Roberto Ravazzolo; Marco Seri; Gianni Camera
- Publisher
- John Wiley and Sons
- Year
- 2003
- Tongue
- English
- Weight
- 125 KB
- Volume
- 117A
- Category
- Article
- ISSN
- 1552-4825
No coin nor oath required. For personal study only.
✦ Synopsis
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. © 2003 Wiley‐Liss, Inc.