The complete spectrum of clinical phenotypes resulting from @entity1120 continues to evolve. While most @entity1 with @entity1120 have residual glucocerebrosidase activity, we describe a fetus with severe prenatal @entity1605 (acute neuronopathic) @entity1120 lacking glucocerebrosidase activity. This 22-week fetus was the result of a first cousin marriage and had @entity4 , external abnormalities, @entity828 , and Gaucher cells in several organs. Fetal fibroblast DNA was screened for common Gaucher mutations, none of which was detected. Southern blot analysis using the restriction enzymes SstII and SspI ruled out a fusion gene, deletion, or duplication of either allele, and quantitative studies of SspI digested genomic DNA indicated that both alleles were present. Northern blot analysis of total RNA from fetal fibroblasts demonstrated no detectable transcription, although RT-PCR successfully amplified several exons, suggesting the presence of a very unstable mRNA. Direct PCR sequencing of all exons demonstrated a homozygous frameshift mutation (deletion of a C) on codon 139 in exon 5, thereby introducing a premature termination codon in exon 6. The absence of glucocerebrosidase protein was confirmed by Western analysis. This unique case confirms the essential role of glucocerebrosidase in @entity1 development and, like the null allele Gaucher @entity19 , demonstrates the lethality of a homozygous null mutation. The presence of this novel mutation and the resulting unstable mRNA accounts for the severity of the phenotype observed in this fetus, and contributes to the understanding of genotype/phenotype correlation in @entity1120 .

Prenatal lethality of a homozygous null mutation in the XXXX glucocerebrosidase gene.

@entity1 :: ('9606', 'Species') :: ['human', 'patients'] @entity1605 :: ('OMIM:217000', 'Disease') :: ['lethal type 2'] @entity19 :: ('10090', 'Species') :: ['mouse'] @entity4 :: ('MESH:D004487', 'Disease') :: ['hydrops'] @entity828 :: ('MESH:C535727', 'Disease') :: ['hepatosplenomegaly'] @entity1120 :: ('MESH:D005776', 'Disease') :: ['Gaucher disease', 'glucocerebrosidase deficiency']
@entity1 :: (9606,Species) :: ['human']
