Acid sphingomyelinase gene and diagnosis of Niemann-Pick disease
AssigneeMount Sinai School of Medicine of the City University of New York
InventorsEdward H. Schuchman, Robert J. Desnick
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Abstract
The present invention relates to the acid sphingomyelinase gene and to methods of diagnosing Niemann-Pick disease. It is based, at least in part, on the cloning and expression of the full-length cDNA encoding acid sphingomyelinase, the cloning and characterization of the genomic structure of the acid sphingomyelinase gene, and on the discovery of frequent mutations in the acid sphingomyelinase gene of Ashkenazi Jewish Niemann-Pick disease patients.
Claims36
A method of diagnosing Type A or B Newmann-Pick disease in a patient, comprising detecting a recessive mutation in the acid sphingomyelinase gene which results in an alteration of at least one amino acid in the acid sphingomyelinase polypeptide sequence set forth in SEQ ID NO. 33, wherein the detection of the mutation indicates Type A or B Niemann-Pick disease in the patient.
A method for identifying a person as having the potential to genetically transmit Type A or B Niemann-Pick disease comprising detecting a recessive mutation in the acid sphingomyelinase gene in a nucleic sample of the person, which results in an alteration of at least one amino acid in the acid sphingomyelinase polypeptide sequence set forth in SEQ ID NO. 33, wherein the detection of the mutation identifies the person having the potential to genetically transmit Type A or B Niemann-Pick disease.
A kit for identifying a recessive mutation in the acid sphingomyelinase gene resulting in an alteration of at least one amino acid in the acid sphingomyelinase polypeptide sequence set forth in SEQ ID NO:33 comprising at least one oligonucleotide primer having a nucleotide sequence complementary to a portion of the nucleic acid sequence set forth in SEQ ID NO:32 and at least one oligonucleotide primer having a nucleotide sequence identical to a portion of the nucleic acid sequence set forth in SEQ ID NO:32 so that when a human nucleic acid sample is subjected to a polymerase chain reaction utilizing the oligonucleotide primers the portion of the acid sphingomyelinase gene containing the mutation is selectively amplified.
A kit for detecting the R496L or .DELTA.R608 mutation in the acid sphingomyelinase gene comprising at least one oligonucleotide primer having a nucleotide sequence complementary to a portion of the nucleic acid sequence set forth in SEQ ID NO:32 and at least one oligonucleotide primer having a nucleotide sequence identical to a portion of the nucleic acid sequence set forth in SEQ ID NO:32 so that when a human nucleic acid sample is subjected to a polymerase chain reaction utilizing the oligonucleotide primers a portion of the acid sphingomyelinase gene containing the R496L or .DELTA.R608 mutation is selectively amplified.
A kit for detecting the L302P mutation in the acid sphingomyelinase gene comprising at least one oligonucleotide primer having a nucleotide sequence complementary to a portion of the nucleic acid sequence set forth in SEQ ID NO:32 and at least one oligonucleotide primer having a nucleotide sequence identical to a portion of the nucleic acid sequence set forth in SEQ ID NO:32 so that when a human nucleic acid sample is subjected to a polymerase chain reaction utilizing the oligonucleotide primers a portion of the acid sphingomyelinase gene containing the L302P mutation is selectively amplified.
A kit for detecting the fsP330 mutation in the acid sphingomyelinase gene comprising at least one oligonucleotide primer having a nucleotide sequence complementary to a portion of the nucleic acid sequence set forth in SEQ ID NO:32 and at least one oligonucleotide primer having a nucleotide sequence identical to a portion of the nucleic acid sequence set forth in SEQ ID NO:32 so that when a human nucleic acid sample is subjected to a polymerase chain reaction utilizing the oligonucleotide primers a portion of the acid sphingomyelinase gene containing the fsP330 mutation is selectively amplified.
A kit for detecting the R496L, .DELTA.R608, L302P, or fsP330 mutations comprising oligonucleotide primers:
- (SEQ ID NO:1) P1 (5'-AGTAGTCTCGAGACGGGACAGACGAACCA-3') and
- (SEQ ID NO:2) P2 (5'-AGTAGTCTGCAGAGCAGGGTACATGGCACTG-3'), for detecting the L302P mutation;
- (SEQ ID NO:3) P3 (5'-ATCATCAAGCTTGGGTAACCATGAAAGCA-3') and
- (SEQ ID NO:4) P4 (5'-ATCATCGAATTCTACAATTCGGTAATAATTCC-3'), for detecting the fsP330 mutation;
- and
- (SEQ ID NO:6) P6 (5'-AGTAGTGTCGACTTGCCTGGTTGAACCACAGC-3') and
- (SEQ ID NO:7) P7 (5'-AGTAGTCGACATGGGCAGGATGTGTGG-3'), for detecting the R496L or .DELTA.R608 mutations.
Dependencies are inferred from the claim text.