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Case Reports in Genetics
Volume 2011, Article ID 703497, 3 pages
Case Report

Novel Sonic Hedgehog Mutation in a Couple with Variable Expression of Holoprosencephaly

1Genetics Department, Instituto Nacional de Perinatología, Montes Urales 800. Col. Lomas Virreyes, 11000 México, DF, Mexico
2Genetics Department and Research Unit, Instituto de Oftalmología “Conde de Valenciana”, Avenida Chimalpopoca 14, Colonia Obrera, 06800 México, DF, Mexico
3Genetics Department, Hospital General de México, Dr. Balmis 148, 06726 Mexico, DF, Mexico

Received 24 June 2011; Accepted 13 July 2011

Academic Editors: B. Mittal and P. Saccucci

Copyright © 2011 M. Aguinaga et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Holoprosencephaly (HPE) is the most common developmental defect of the forebrain and midface in humans. sporadic and inherited mutations in the human sonic hedgehog (SHH) gene cause 37% of familial HPE. A couple was referred to our unit with a family history of two spontaneous first trimester miscarriages and a daughter with HPE who presented early neonatal death. The father had a repaired median cleft lip, absence of central incisors, facial medial hypoplasia, and cleft palate. Intelligence and a brain CT scan were normal. Direct paternal sequencing analysis showed a novel nonsense mutation (W127X). Facial characteristics are considered as HPE microforms, and the pedigree suggested autosomal dominant inheritance with a variable expression of the phenotype. This study reinforces the importance of an exhaustive evaluation of couples with a history of miscarriages and neonatal deaths with structural defects.