MOLECULAR CYTOGENETIC ANALYSIS OF PATIENTS WITH HOLOPROSENCEPHALY ANDSTRUCTURAL REARRANGEMENTS OF 7Q

The holoprosencephaly (HPE) sequence is a malformation complex with ab normal midline cleavage of the embryonic forebrain. HPE is genetically heterogeneous with at least 6 different chromosome regions containing genes involved in the expression of the phenotype. HPE3, recently ide ntified as the human Sonic hedgehog gene, is localized to 7q36. We hav e used fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR) amplification in 5 cell lines from patients with HPE (3 cases), HPE and sacral agenesis (1 case), and microcephaly (1 case) t o further define the structural rearrangements of the long arm of chro mosome 7 in each case. All cell lines demonstrated loss of material in the critical region of HPE3 at band 7q36, which includes the Sonic he dgehog gene, We report here the analysis of these patient cell lines. (C) 1998 Wiley-Liss, Inc.