Gene mutations at the low density lipoprotein (LDL) receptor locus were screened in 210 alleles of Japanese patients with familial hypercholesterolaemia (FH). In the present study, two types of novel mutation were identified by genomic Southern blotting using human LDL receptor cDNA probes. An approximately 12 kb deletion including exons 2 and 3 (and possibly 4) was identified in a patient (M.I.). The patient with this mutant gene will be referred to as 'FH-Kanazawa'. Two patients born in Okayama Prefecture in Japan had another unique 13 kb partial deletion, from exons 7 to 14, in their LDL receptor genes (FH-Okayama). This mutant allele is the first reported case in which the central portion of the LDL receptor gene, the epidermal growth factor (EGF) precursor homology region, is eliminated.