AGENESIS OF THE CORPUS-CALLOSUM WITH PROBST BUNDLES OWING TO HAPLOINSUFFICIENCY FOR A GENE IN AN 8 CM REGION OF 6Q25

Agenesis of the corpus callosum (ACC) is a relatively common brain abn ormality resulting from developmental defects either limited to the st ructures leading to the proper formation of the corpus callosum or inv olving the embryo forebrain more generally. ACC is genetically heterog eneous with autosomal dominant, autosomal recessive, and X linked inhe ritance and has also been reported in subjects with aneuploidies invol ving several chromosomes. Among them, distal 691 deletions have been c onsistently reported in association with ACC, suggesting that there is a gene in the deleted region whose haploinsufficiency impairs normal corpus callosum development. We have studied a child with ACC with Pro bst bundles and a deletion at 6q25 of about 8 cM, from D6S1496 to D6S4 37. Probst bundles are the axons that should have formed the corpus ca llosum but, unable to cross the midline owing to absence of the massa commissuralis, they run longitudinally along the medial walls of the . lateral ventricles from the frontal to the occipital lobes. Thus, thei r presence suggests that a gene located in the 6q deleted region is sp ecifically involved in the formation of the massa commissuralis and th at its haploinsufficiency leads to primary ACC.