DETECTING DELETIONS IN THE CRITICAL REGION FOR LISSENCEPHALY ON 17P13.3 USING FLUORESCENT IN-SITU HYBRIDIZATION AND A PCR ASSAY IDENTIFYINGA DINUCLEOTIDE REPEAT POLYMORPHISM

During a study of lissencephaly in England and Wales, 23 children were identified with this diagnosis. They were classified as follows: thre e children had Miller-Dieker syndrome (MDS), 13 had isolated lissencep haly sequence (ILS), two had type II lissencephaly, and live children were reclassified as focal or diffuse cortical dysplasia. Microdeletio ns of chromosome 17p13.3, also known as the Miller-Dieker critical reg ion, have been associated with both MDS and ILS. We used the commercia lly available Oncor probe for fluorescent in situ hybridisation (FISH) studies on 14 patients and a further four were studied elsewhere. Del etions were identified in all three MDS patients and two of the ILS pa tients. These results are consistent with previously reported data. No deletions were found in those patients with focal or diffuse cortical dysplasia. In addition, a CA repeat polymorphism which maps to the Mi ller-Dieker critical region was studied in 12 families and was informa tive in nine; the results were consistent with the FISH data. We concl ude that FISH is a reliable method to detect deletions in patients wit h MDS and ILS and also useful to identify chromosome rearrangements in their parents which are not detected by conventional cytogenetic anal ysis. The PCR assay, if informative, is also, reliable and a useful al ternative if only DNA is available. None of the five children with aty pical radiological features had a deletion. We therefore suggest that as well as looking for other aetiologies a careful review of the diagn osis should be made of the MDS or ILS cases in whom a deletion is not found.