Glucocerebrosidase mutations among African-American patients with type 1 Gaucher disease

While the inherited deficiency of the enzyme glucocerebrosidase (Gaucher di sease) is panethnic in its distribution, there :have not been studies of th e mutations encountered in specific ethnic groups in the United States, oth er than those on Ashkenazi Jews, We present the clinical descriptions and g enotypes of seven patients of African-American ancestry with type 1 Gaucher disease, and summarize the published literature regarding the genotypes en countered in this population. All seven of the patients had moderate-to-sev ere manifestations of the disease, and all developed symptoms by adolescenc e. Genotypic analyses revealed that no two probands shared the same genotyp e, The common mutations N370S, c.84-85insG, IVS2+1 G--> A, and R463C were n ot seen. Mutation L444P was present on one allele in each of the patients: but the same mutation was encountered as a single point mutation in three o f the patients, and as part of a recombinant allele in four of the patients . Southern blot analyses revealed a glucocerebrosidase fusion allele in one patient, and a duplication resulting from recombination in the region down stream from the glucocerebrosidase gene in three of the patients. Five diff erent point mutations (A90T, R48W, N117D, R170C, and V352L), one deletion m utation (c.222-224 delTAC), and one insertion mutation (c.153-154 insTACAGC ) were encountered. Our results demonstrate that there is significant genot ypic heterogeneity among African-American patients with type 1 Gaucher dise ase, and that recombinations in the glucocerebrosidase gene locus are parti cularly common in this patient group. Published 2001 Wiley-Liss, Inc.(dagge r)