Polymorphism MI detected through the enzyme MspI in the study of congenital protein C deficiency

BACKGROUND: In order to find alternatives for the diagnosis of hereditary protein C (PC) deficiency, we have studied the diagnostic informativity of the restriction fragment length polymorphism (RFLP) MI, located 7 kb upstream of the PC gene and detected with the restriction enzyme MspI. METHODS: The RFLP MI has been analysed in 77 individuals belonging to 27 families with congenital PC deficiency, as well as in a control group of 46 healthy donors. The analysis has been performed by PCR amplification and MspI digestion of the polymorphic DNA fragment. RESULTS: The allelic frequencies of the RFLP MI in the population studied are 0.69 for the allele A1, without the MspI restriction site, and 0.31 for the allele A2, with the MspI site. No differences have been found between the control and the PC deficient groups. The informativity of the polymorphism has been calculated to be 33.8%. Consegregation studies between this RFLP and PC deficiency have allowed the determination of the allele associated to the polymorphism in 21 out of the 27 studied families. Furthermore, an asymptomatic PC deficient carrier, with normal PC levels, has been identified. CONCLUSIONS: The study of this RFLP in families with hereditary PC deficiency may be useful for the identification of PC deficient carriers as well as for the prenatal diagnosis of the deficiency.