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Holoprosencephaly in a family segregating novel variants in ZIC2 and GLI2
Author(s) -
Wannasilp Nilrat,
Solomon Benjamin D.,
WarrenMora Nicole,
Clegg Nancy J.,
Delgado Mauricio R.,
Lacbawan Felicitas,
Hu Ping,
Winder Thomas L.,
Roessler Erich,
Muenke Maximilian
Publication year - 2011
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.33903
Subject(s) - holoprosencephaly , penetrance , genetics , gli2 , gene , biology , inheritance (genetic algorithm) , craniofacial , population , expressivity , sonic hedgehog , phenotype , medicine , pregnancy , fetus , environmental health
Holoprosencephaly (HPE) is the most common malformation of the human forebrain. Typical manifestations in affected patients include a characteristic pattern of structural brain and craniofacial anomalies. HPE may be caused by mutations in over 10 identified genes; the inheritance is traditionally viewed as autosomal dominant with highly variable expressivity and incomplete penetrance. We present the description of a family simultaneously segregating two novel variants in the HPE‐associated genes, ZIC2 and GLI2 , as well as the results of extensive population‐based studies of the variant region in GLI2 . This is the first time that multiple HPE‐associated variants in these genes have been reported in one family, and raises important questions about how clinicians and researchers should view the inheritance of conditions such as HPE. © 2011 Wiley‐Liss, Inc.