Homozygous loss of a cysteine residue in the glucocerebrosidase gene results in Gaucher's disease with a hydropic phenotype

Acute neuronopathic Gaucher's disease is classically considered to be a disease of late infancy, but also includes a spectrum of variant phenotypes such as perinatal lethal hydrops, or the collodian baby phenotype in the newborn period. These extreme phenotypes are frequently associated with recombinant alleles, nonsense mutations and rare missense mutations. In this report, we present a family with multiple incidence of a hydrops where Gaucher's disease was confirmed. Mutational analysis revealed the homozygosity for the missense mutation C16S, which is located in exon 3 and results in the loss of a cysteine residue. This genotype would be predicted to result in virtually zero enzyme activity.