ARX and SHH gene mutation analyses revealed no mutation in patients with agenesis/dysgenesis of the corpus callosum

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.