Abstract
Mevalonate kinase deficiency (MKD), an inborn error of sterol synthesis, presents with clinical variability. To define a genetic basis for this variability, we determined MK activity in fibroblast heterokaryons obtained from polyethylene glycol fusion. Fusion of control fibroblasts with 6 MKD cell lines yielded positive complementation (37% of control activity). None of the fusions between the 6 MKD cell lines yielded detectable MK activity. Michaelis constants in an MK assay optimized for use in biopsied chorionic villi (BCV) were 0.06 and 0.7 mM for mevalonate and ATP, respectively. MK activity in control BCV increased linearly (0.8-4.3 nmol/min/mg protein) with gestational age from 7 to 14 weeks. MK activity in BCV from a pregnancy at risk for MKD was 430 pmol/min/mg protein, suggesting an unaffected fetus. We conclude there is no evidence for genetic heterogeneity in MKD which would explain the variability in clinical expression. The availability of an optimized MK assay for use in BCV allows reliable 1st trimester prenatal diagnosis for families at risk.
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Gibson, K., Hoffmann, G. 125 GENETIC COMPLEMENTATION ANALYSIS OF MEVALONATE KINASE DEFICIENCY IN CULTURED FIBROBLASTS. Pediatr Res 30, 649 (1991). https://doi.org/10.1203/00006450-199112000-00155
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DOI: https://doi.org/10.1203/00006450-199112000-00155