Abstract
The LDL receptor gene mutations of FH patients from 190 unrelated Japanese families were screened and the following results were obtained:
1. Four types of new variants were identified through Southern blotting.
i) FH-Tonami-1 with 6 kb deletion (exon 15) was found in 6 families. Neonatal diagnosis of FH in three fetuses from one family was possible through the analysis of their LDL receptor genes.
ii) FH-Okayama with 13kb deletion (exon 7-13) was found in 2 families.
iii) FH-Kanazawa with 12 kb deletion (exon 2 and 3) was found in 1 family.
iv) FH-Tonami-2 with 10kb deletion (exon 2 and 3) was found in 9 families. Abnormal LDL receptors produced by this mutant gene possessed half the activity of normal receptors. Both homozygous and heterozygous patients with this gene mutation showed mild clinical manifestations and longevity influences in comparison with “classical” FH patients.
2. A majority (90%) of Japanese FH patients had small gene mutations in their LDL receptor genes.
