Mutation in the sphingolipid activator protein 2 in a patient with a variant of Gaucher disease

Abstract

The lysosomal degradation of glucosylceramide requires the hydrolase, glucosylceramide‐β‐glucosidase and a sphingolipid activator protein (Gaucher factor, SAP‐2, saposin C). Genetic defects in either of these lysosomal proteins cause phenotypically similar disorders in man, the Gaucher disease. SAP‐2 originates from a gene which generates a mRNA that codes for four homologous proteins. In a patient with an immunologically proven SAP‐2 deficiency a G¹¹⁵⁴ → T transversion (counted from A of the initiation codon ATG) was found in the mRNA of the SAP‐2 precursor which results in the substitution of Phe for Cys³⁸⁵ in the mature SAP‐2. The rest of the coding sequence remained entirely normal.