A NUMBER OF SCHIZENCEPHALY PATIENTS INCLUDING 2 BROTHERS ARE HETEROZYGOUS FOR GERMLINE MUTATIONS IN THE HOMEOBOX GENE EMX2

We report here that some patients affected by schizencephaly are heter ozygous for mutations in EMX2, a homeobox gene implicated in the patte rning of the developing forebrain, Schizencephaly is a very rare human congenital disorder characterized by a full-thickness cleft within th e cerebral hemispheres. Large portions of these may be absent and repl aced by cerebrospinal fluid. We previously reported the presence of EM X2 mutations in 7 out of 8 sporadic cases of schizencephaly. We now ex tend this analysis to 10 additional patients, including 2 brothers. Si x patients were found to be heterozygous for de novo mutations in EMX2 . In particular, the 2 brothers show the same mutation affecting the s plicing of the first intron,while this mutation is absent in their par ents and in the 2 unaffected siblings.