Niemann-Pick disease type C: Genetic heterogeneity

Journal Article · Thu Sep 01 04:00:00 EDT 1994 · American Journal of Human Genetics

OSTI ID:133976

Vanier, M T; Duthel, S; Rodriguez-Lafrasse, C ^[1]

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1. Lyon-Sud Medical School, Oullins (France); and others

Although the primary defect is yet unknown, Niemann-Pick disease type C is at present best defined by unique abnormalities of intracellular translocation of exogenous cholesterol. A considerable variation in severity of clinical and biochemical expression has been described: nevertheless, our first genetic complementation study including eleven unrelated patients of varying phenotypes indicated that they all belonged to a single complementation group. We recently mapped the gene responsible for this major group to chromosome 18. In a recent meeting, Fensom and associates reported complementation between the cell line from one patient and those from seven other families. In conjunction with linkage studies, we have now expanded our investigation to the study of 28 unrelated patients. We have found that cell lines from 3 of those patients were able to complement the defect (intralysosomal storage of cholesterol evaluated by filipin staining) in cell lines from the main complementation group (25/28), and did not complement among themselves. Two of the patients had presented with a severe rapidly fatal clinical form while the two affected members in the third family had a slow progressive juvenile phenotype. They all belonged to the classical (severe) biochemical phenotype and had different ethnic origin. Since we learned that one of those cases was the same as that studied by Fensom (personal communication), all Niemann-Pick type C patients studied so far can be divided into two complementation groups. Using microsatellite markers in our multiplex family, we could further show that the gene responsible for the second minor complementation group does not map to the location of the major gene.

• OSTI ID: 133976
• Report Number(s): CONF-941009--
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
BIOLOGICAL MARKERS
CHOLESTEROL
GENES
GENETIC MAPPING
GENETICS
HEREDITARY DISEASES
HUMAN CHROMOSOME 18
LYSOSOMES
METABOLIC DISEASES
METABOLISM
PATIENTS
PHENOTYPE
STATISTICS
STORAGE