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

The finding of extensive lytic lesions in the mandible of a 19‐year‐old Ashkenazi Jewish woman led to the diagnosis of Type 1 Gaucher disease. She had extensive skeletal involvement, marked hepatosplenomegaly, and deficient acid β‐glucosidase activity. Mutation analysis identified heteroallelism for acid β‐glucosidase mutations N370S and P401L, the latter being a novel missense mutation in exon 9. Expression of the P401L allele resulted in an enzyme with a reduced catalytic activity (specific activity based on cross‐reacting immunological material ∼0.21), which was similar to that of the mild N370S mutant enzyme. The expression studies predicted a mild phenotype for the proposita's N370S/P401L genotype which was inconsistent with her severe diffuse skeletal disease and organ involvement. Since lytic mandibular lesions may be complicated by osteomyelitis, pathologic fracture, and tooth loss, regular dental assessments in Type 1 Gaucher patients should be performed. Am. J. Med. Genet. 84:334–339, 1999. © 1999 Wiley‐Liss, Inc.