Type 1 Gaucher disease presenting with extensive mandibular lytic lesions:Identification and expression of a novel acid beta-glucosidase mutation

The finding of extensive lytic lesions in the mandible of a 19-year-old Ash kenazi Jewish woman led to the diagnosis of Type 1 Gaucher disease. She had extensive skeletal involvement, marked hepatosplenomegaly, and deficient a cid p-glucosidase activity. Mutation analysis identified heteroallelism for acid P-glucosidase mutations N370S and P401L, the latter being a novel mis sense mutation in exon 9, Expression of the P401L allele resulted in an enz yme with a reduced catalytic activity (specific activity based on cross-rea cting immunological material similar to 0.21), which was similar to that of the mild N370S mutant enzyme, The expression studies predicted a mild phen otype for the proposita's N370S/P401L genotype which was inconsistent with her severe diffuse skeletal disease and organ involvement. Since lytic mand ibular lesions may be complicated by osteomyelitis, pathologic fracture, an d tooth loss, regular dental assessments in Type 1 Gaucher patients should be performed, (C) 1999 Wiley-Liss, Inc.