Two partial deletion mutations involving the same Alu sequence within intron 8 of the LDL receptor gene in Korean patients with familial hypercholesterolemia.

摘要: Twenty-eight unrelated persons heterozygous for familial hypercholesterolemia (FH) were screened to assess the frequency and nature of major structural rearrangements at low-density lipoprotein (LDL) receptor gene in Korean FH patients. Genomic DNA was analyzed by Southern blot hybridization with probes encompassing exons 1–18 LDL gene. Two different deletion mutations (FH29 FH110) detected three patients (10.7%). Each characterized use exon-specific detailed restriction mapping mediated long-PCR (polymerase chain reaction). Mutation FH29 a 3.83-kb extending from intron 6 8 FH110 5.71-kb 12. In FH29, translational reading frame preserved deducible result cysteine-rich A B repeat truncated protein that might be unable bind but would continue β-VLDL. is presumed null allele, since shifts results terminates exon 13. Sequence analysis revealed both deletions have occurred between two Alu-repetitive sequences are same orientation. This suggested these caused an unequal crossing over event following mispairing Alu on chromatids during meiosis. Moreover, deletions, recombinations related sequence breakpoints found within specific sequence, 27 bp length. supports hypothesis this region some intrinsic instability, act as one important factors large recombinational rearrangements.