Gaucher disease is inherited in an autosomal recessive manner and is the most 
prevalent lysosomal storage disease. Gaucher disease has marked phenotypic 
variation and molecular heterogeneity, and several simple and complex alleles of 
the acid beta-glucosidase gene have been identified as causal to this disease. 
Certain combinations of alleles have been shown to correlate well with the 
severity of the disease, but many Gaucher disease patients exist whose disease 
is not explained by any of the published mutations. This study was undertaken to 
identify mutant alleles in such incompletely characterized Gaucher disease, in 
an attempt to find further correlations between clinical phenotype and the 
presence of acid beta-glucosidase alleles. RNA was isolated from Gaucher cell 
lines and converted to cDNA, the cDNA was amplified by PCR and cloned, and 
several clones for each allele were sequenced. Several new singly mutated and 
multiply mutated alleles were identified, and sequence-specific oligonucleotide 
hybridization was used to verify the presence of these mutations in the genome 
of these patients. All newly identified mutations occurred only rarely in the 
Gaucher disease population, making it difficult to determine whether inheritance 
of a particular combination of alleles always correlates with the clinical 
manifestations seen in the test patients. Three of the newly described alleles 
were single missense mutations in exon 8, one was a single missense mutation in 
exon 5, and the fifth was a complex allele, comprising a series of different 
point mutations scattered throughout exons 5 and 6.(ABSTRACT TRUNCATED AT 250 
WORDS)