SEGREGATION OF THE N301T MUTATION IN THE FAMILY OF THE INDEX PATIENT WITH MEVALONATE KINASE-DEFICIENCY

Inherited deficiency of mevalonate kinase (MK), an enzyme of the chole sterol biosynthetic pathway, has been described in 11 patients (Hoffma nn et al 1993). Of these 11, a disease-causing mutation has been ident ified only in the index patient (Schafer et al 1992). Direct sequencin g of cDNAs encoding MK obtained from a fibroblast cDNA library of the index patient revealed a missense mutation (A --> C) at nucleotide 902 of the open reading frame, resulting in an asparagine (N) to threotin e (T) substitution (N301T). The inheritance of this mutation was confi rmed by PCR amplification and allele-specific oligonucleotide (ASO) hy bridization of genomic DNAs from the parents and sibling of the proban d (Schafer et al 1992). The father and brother expressed the N301T mut ation, but the mother did not, indicating that the index patient was a compound heterozygote. We extend these earlier studies by analysing t he segregation of the N301T mutation in genomic DNA obtained from 23 f amily members of the index proband using ASO hybridization.