Affiliations: Institute of Social Pediatrics and Adolescent
Medicine, University of Munich, Munich, Germany | Institute of Clinical Radiology, University of Munich,
Munich, Germany | Center for Human Genetics, Regensburg, Germany | Practice of Human Genetics, Berlin, Germany
Note: [] Correspondence: Dr. Chayim Can Schell-Apacik, MD, Practice of
Human Genetics, Spandauer Damm 130 – 14050 Berlin, Germany. Tel.: +49 30 3035
5778; Fax: +49 30 3035 5779; E-mail: [email protected]
Abstract: Mutations in sonic hedgehog (SHH; OMIM *600725) and the
aristaless-related homeobox gene (ARX; OMIM *300382) can both result in
severe brain malformation. Haploinsufficiency of SHH has been shown to
cause not only midline structure defects such as holoprosencephaly, corpus
callosum agenesis but also developmental delay and/or craniofacial dysmorphic
features including microcephaly, hypotelorism, or a single central incisor.
Mutations in the ARX gene may result in different phenotypes as well,
such as X-linked mental retardation (XLMR; OMIM #300419), X-linked
lissencephaly with ambiguous genitalia (XLAG; OMIM #300215), Partington
syndrome (OMIM #309510), X-linked myoclonic epilepsy (OMIM #300432),
X-linked West syndrome (OMIM #308350), and agenesis of the corpus callosum
with abnormal genitalia (OMIM #300004). In a total number of 27 patients
with complete or partial absence of the corpus callosum, SHH and
ARX genes were investigated in order to evaluate whether mutations in
SHH and ARX result in partial (dysgenesis) or complete (agenesis)
absence of the corpus callosum. No causative mutations could be detected
suggesting that these genes may not play a major role in corpus callosum formation.
Keywords: Sonic hedgehog, aristaless-related homeobox gene, agenesis and dysgenesis of the corpus callosum
