A compound heterozygote for familial hypercholesterolaemia with a homozygous mother

Homozygous familial hypercholesterolaemia (FH) is a rare disorder in which the patients develop severe hypercholesterolaemia and premature coronary atherosclerosis from childhood. Here we report a unique family with clustering of homozygous FH. The proband was a 25-year-old man, who showed marked hypercholesterolaemia, multiple xanthomas and severe coronary atherosclerosis. His mother also showed the typical characteristics of homozygous FH. Sequencing analysis of the low-density lipoprotein receptor gene revealed that he was a compound heterozygote, carrying two different point mutations. One was a novel mutation, FH Wakayama (Cys-->Ser at 317), derived from his mother, and the other was a recurrent mutation, FH Niigata (T-->C at 1845 + 2, 5' splice signal in intron 12), derived from his father. The proband we report seems to be a very rare case of an FH homozygote born from a homozygous mother.