Compound heterozygosity at the sphingomyelin phosphodiesterase-1 (SMPD1) gene is associated with low HDL cholesterol

Type A and B forms of Niemann-Pick disease (NPD) are lipid storage disorders caused by deficient activity of the enzyme acid sphingomyelinase (aSMase) and the resulting accumulation of sphingomyelin in tissues. In the present study, we investigated two family members who had been diagnosed with Type...

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Bibliographic Details
Published in:Human genetics 2003-05, Vol.112 (5-6), p.552-562
Main Authors: CHING YIN LEE, KRIMBOU, Larbi, VINCENT, Jérome, BERNARD, Chantal, LARRAMEE, Pierre, GENEST, Jacques JR, MARCIL, Michel
Format: Article
Language:English
Subjects:
acid sphingomyelinase
Biological and medical sciences
Blood cholesterol
Cholesterol, HDL - blood
Cholesterol, HDL - genetics
Cholesterol, HDL - metabolism
coronary artery disease
Coronary heart disease
Enzymes
Ethylenediaminetetraacetic acid
Female
Fundamental and applied biological sciences. Psychology
Genes
Genetic aspects
Health aspects
Heterozygote
Humans
Male
Medical research
Medicine, Experimental
Molecular and cellular biology
Niemann-Pick Diseases - enzymology
Niemann-Pick Diseases - genetics
Niemann-Pick Diseases - physiopathology
Pedigree
Phospholipids
Sequence Analysis, DNA
sphingomyelin
Sphingomyelin Phosphodiesterase - genetics
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Summary:Type A and B forms of Niemann-Pick disease (NPD) are lipid storage disorders caused by deficient activity of the enzyme acid sphingomyelinase (aSMase) and the resulting accumulation of sphingomyelin in tissues. In the present study, we investigated two family members who had been diagnosed with Type B NPD and who had a severe decrease in plasma high density lipoprotein cholesterol (HDL-C). The proband (a 48-year-old male) had an HDL-C of 0.30 mmol/l (12 mg/dl) and his sister had values of 0.45 mmol/l (17 mg/dl) with severe premature coronary artery disease (CAD). Hypertriglyceridemia was found in both cases. aSMase activity measured in skin fibroblasts appeared markedly depressed. The SMPD1 gene, coding for aSMase, was sequenced in affected subjects and all family members. Compound heterozygosity (DeltaR608 and R441X) was identified in both affected patients. Carriers of the DeltaR608 mutation tended to have moderately to severe decreased HDL-C levels, whereas carriers of the R441X mutation, although present only in young subjects (
ISSN:0340-6717
1432-1203
DOI:10.1007/s00439-002-0893-1