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

2003; Wiley; Volume: 117A; Issue: 2 Linguagem: Inglês

10.1002/ajmg.a.10163

1552-4833

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

Oral and Maxillofacial Pathology

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.