Simultaneous deficiency of sphingolipid activator proteins 1 and 2 is caused by a mutation in the initiation codon of their common gene.
Sphingolipid activator proteins (SAPs) are small, nonenzymic glycoproteins that stimulate lysosomal degradation of various sphingolipids. SAP-1, SAP-2, and two additional potential activator proteins are derived from a common precursor by proteolytic processing. A severe case of sphingolipid storage disease that led to death within 16 weeks was attributed to a possible total deficiency of the SAPs generated by this gene (Harzer, K., Paton, B. C., Poulos, A., Kustermann-Kuhn, B., Roggendorf, W., Grisar, T., and Popp, M. (1989) Eur. J. Pediatr. 149, 31-39). Analysis of the SAP precursor cDNA from the patient and his fetal sibling showed an A to T transversion in the initiation codon. Allele-specific oligonucleotide hybridization revealed that both parents are heterozygous carriers for this mutation. In pulse-chase experiments using antisera raised against SAP-1 or SAP-2, no cross-reacting material could be detected in the patients' fibroblasts.
Institute of Organic Chemistry and Biochemistry, University of Bonn, Germany.
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D
Schnabel
M
M
Schröder
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W
Fürst
A
A
Klein
R
R
Hurwitz
T
T
Zenk
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J
Weber
K
K
Harzer
B C
BC
Paton
A
A
Poulos
D000483:Alleles; D001483:Base Sequence; D002478:Cells, Cultured; D003062:Codon / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism; D006023:Glycoproteins / Q000172:deficiency / Q000235:genetics*; D006801:Humans; D008052:Lipid Metabolism, Inborn Errors / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D049231:Saposins; D012867:Skin / Q000378:metabolism; D049128:Sphingolipid Activator Proteins
D003062:Codon; D006023:Glycoproteins; D009838:Oligodeoxyribonucleotides; C483345:PSAP protein, human; D049231:Saposins; D049128:Sphingolipid Activator Proteins; D012313:RNA