Niemann-Pick disease: A frequent missense mutation in the acid sphingomyelinase gene of Ashkenazi Jewish type A and B patients

Journal Article · Wed May 01 00:00:00 EDT 1991 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.88.9.3748· OSTI ID:6096583

Levran, O; Desnick, R J; Schuchan, E H ^[1]

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1. Mount Sinai School of Medicine, New York, NY (United States)

Although the A and B subtypes of Niemann-Pick disease (NPD) both result from the deficient activity of acid sphingomyelinase and the lysosomal accumulation of sphingomyelin, they have remarkably distinct phenotypes. Type A disease is a fatal neurodegenerative disorder of infancy, whereas type B disease has no neurologic manifestations and is characterized primarily by reticuloendothelial involvement and survival into adulthood. Both disorders are more frequent among individuals of Ashkenazi Jewish ancestry than in the general population. The recent isolation and characterization of cDNA and genomic sequences encoding ASM has facilitated investigation of the molecular lesions causing the NPD subtypes. Total RNA was reverse-transcribed, and the ASm cDNA from an Ashkenazi Jewish type A patient was specifically amplified by the polymerase chain reaction (PCR). Molecular analysis of the PCR products revealed a G{r arrow} T transversion of nucleotide 1,487, which occurred at a CpG dinucleotide and predicted an Arg{r arrow} Leu substitution and that both parents and several other relatives were heterozygous. These findings identify a frequent missense mutation among NPD patients of Ashkenazi Jewish ancestry that results in neuronopathic type A disease when homoallelic and can result in the nonneuronopathic type B phenotype when heteroallelic. The identification of this ASM mutation in Ashkenazi Jewish patients should facilitate the prevention of NPD in this population by carrier detection with molecular diagnostic techniques.

• OSTI ID: 6096583
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Vol. 88:9; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ESTERASES
GENE MUTATIONS
HEREDITARY DISEASES
ETIOLOGY
DNA BASE TRANSITIONS
DNA POLYMERASES
FIBROBLASTS
HUMAN POPULATIONS
LYMPHOCYTES
LYSOSOMES
MYELIN
PATIENTS
RECOMBINANT DNA
ANIMAL CELLS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CELL CONSTITUENTS
CELL MEMBRANES
CONNECTIVE TISSUE CELLS
DISEASES
DNA
ENZYMES
HYDROLASES
LEUKOCYTES
MATERIALS
MEMBRANES
MUTATIONS
NUCLEIC ACIDS
NUCLEOTIDYLTRANSFERASES
ORGANIC COMPOUNDS
PHOSPHORUS-GROUP TRANSFERASES
POLYMERASES
POPULATIONS
PROTEINS
SOMATIC CELLS
TRANSFERASES
550400* - Genetics