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

Abstract

While the inherited deficiency of the enzyme glucocerebrosidase (Gaucher disease) is panethnic in its distribution, there have not been studies of the mutations encountered in specific ethnic groups in the United States, other than those on Ashkenazi Jews. We present the clinical descriptions and genotypes of seven patients of African-American ancestry with type 1 Gaucher disease, and summarize the published literature regarding the genotypes encountered in this population. All seven of the patients had moderate-to-severe manifestations of the disease, and all developed symptoms by adolescence. Genotypic analyses revealed that no two probands shared the same genotype. The common mutations N370S, c.84-85insG, IVS2+1 G-->A, and R463C were not 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 of 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 downstream from the glucocerebrosidase gene in three of the patients. Five different point mutations (A90T, R48W, N117D, R170C, and V352L), one deletion mutation (c.222-224 delTAC), and one insertion mutation (c.153-154 insTACAGC) were encountered. Our results demonstrate that there is significant genotypic heterogeneity among African-American patients with type 1 Gaucher disease, and that recombinations in the glucocerebrosidase gene locus are particularly common in this patient group. Published 2001 Wiley-Liss, Inc.

Multi-organ Abnormalities and mTORC1 Activation in Zebrafish Model of Multiple Acyl-CoA Dehydrogenase Deficiency

“…Lysosomal disorders such as metachromatic leukodystrophy (MLD) [30], Krabbe disease [31] and Gaucher disease [32] all have accumulation of cerebroside sulfate that appears to cause myelination defects in nerve system as well as hepatomegaly. We also see accumulation of cerebroside sulfate in radial glia and hepatocytes in dxa mutant larvae.…”

Gaucher's disease: identification of novel mutant alleles and genotype–phenotype relationships

“…Clinical reports (Table 1) Case 1, a 37-year-old African-American male with Gaucher's disease type 1, was diagnosed at age 15. This case may have been reported previously (23). He has been followed at Cincinnati Children's Hospital Medical Center every 6-12 months for the past 10 years.…”

“…The g.2600‐2602delTAC allele could be derived from a reported patient, but in the absence of detailed clinical information this is difficult to ascertain (10, 23). Even if this is the case, more extensive clinical information and sequence data are reported here.…”

Exclusion of NEU1 and PPGB from candidate genes for a lysosomal storage disease in Japanese Black cattle

“…Lysosomal storage diseases are hereditary diseases of humans and other mammalian species characterized by intracellular accumulation of macromolecular substrates caused by deficiency of lysosomal hydrolases. Many different types of lysosomal storage diseases, in which specific substrates are accumulated in tissues have been reported in humans (Bennet et al 1995;Hahn et al 1997;Park et al 2001;Groener et al 2003) and various mutations in the genes encoding these enzymes have been found in patients of these diseases (Myerowitz 1997;Nilssen et al 1997;Park et al 2001;Groener et al 2003). Similar lysosomal storage diseases have been reported in domestic animals, including cattle, sheep, cats, and dogs (Donnelly & Sheahan 1977;Ryder & Simmons 2001;Kanae et al 2007).…”

“…2003) and various mutations in the genes encoding these enzymes have been found in patients of these diseases (Myerowitz 1997; Nilssen et al. 1997; Park et al. 2001; Groener et al.…”