ANGELMAN SYNDROME-ASSOCIATED WITH A MATERNAL 15Q11-13 DELETION OF LESS-THAN 200 KB

Angelman syndrome (AS) is a neurogenetic disorder arising from a lack of genetic contribution from the maternal chromosome 15q11-13. To date , the AS critical region has been defined by an inherited deletion of approximately 1.5Mb, spanning the 3-21 (D15S10), LS6-1 (D15S113) and G ABRB3 loci. We have identified an individual with the typical features of AS who has a deletion of the maternal chromosome which encompasses LS6-1, but does not extend to either flanking marker. This deletion, initially detected by (CA), repeat analysis, was further characterised by fluorescence in situ hybridisation (FISH) using cosmids derived fr om a 260 kb LS6-1 yeast artificial chromosome (YAC). Neither end cosmi d from this YAC clone falls within the deletion, suggesting that the m inimal AS region is less than 200 kb. We also studied three loci withi n 15q11-13 which detect parent-of-origin specific DNA methylation impr ints, and found that both normal maternal and paternal patterns were p resent in this patient.