TheMolecular BasisofCanavan(Aspartoacylase Deficiency) Disease inEuropeanNon-Jewish Patients

Summary Canavan disease isaninfantile neurodegenerative disease that isduetoaspartoacylase deficiency. Thedisease hasbeenreported mainly inAshkenazi Jewsbutalso occurs inother ethnic groups. Determination ofenzymatic activity forcarrier detection andprenatal diagnosisisconsidered unreliable. Inthepresent study, nine mutations werefound intheaspartoacylase geneof19 non-Jewish patients. These included fourpoint mutations (A305E [39.5% ofthemutated alleles], C218X [15.8%], F295S [2.6%], andG274R[5.3%]); four deletionmutations (827delGT [5.3%], 870del4 [2.6%], 566de17 [2.6%], and527de16 [2.6%]); andoneexon skip (527del108 [5.3%]). TheA305Emutation ispanEuropean andprobably themostancient mutation, identified inpatients ofGreek, Polish, Danish, French, Spanish, Italian, andBritish origin. Incontrast, the G274Rand527de1108 mutations werefound only in patients ofTurkish origin, andtheC218Xmutation was identified only inpatients ofGypsy origin. HomozygosityfortheA305Emutation wasidentified inpatients withboththesevere andthemildforms ofCanavan disease. Mutations wereidentified in31ofthe38alleles, resulting inanoverall detection rate of81.6%. Allnine mutations identified innon-Jewish patients reside inexons4-6oftheaspartoacylase gene. Theresults would enable accurate genetic counseling inthefamilies of13 (68.4%) of19patients, inwhomtwomutations were identified intheaspartoacylase cDNA.