Hypobetalipoproteinemia due to an apolipoprotein B gene exon 21 deletion derived by Alu-Alu recombination.

摘要: We report the molecular defect in an individual with homozygous hypobetalipoproteinemia. A unique TaqI restriction fragment length polymorphism was found midportion of apolipoprotein B (apoB) gene using genomic probe, pB51. The which identifies fragments 8.4 and 2.8 kilobases (kb) normal individuals, hybridized to a single 11-kb proband. parents proband showed all three fragments, implying that they are heterozygotes for mutant apoB allele. In this family, allele cosegregated low total cholesterol levels formal linkage analysis gave decimal logarithm ratio score 3.3 at recombination frequency 0. polymorphic site localized EcoRI 4 kb individuals. corresponding 3.4 kb, suggesting 0.6-kb deletion Both 4-kb 3.4-kb were cloned sequenced. allele, extends from intron 20 23. Exon 21 is flanked by Alu sequences same orientation. had 694-bp region included small part sequence 20, entire exon 21, most 21. site, lies within absent as result deletion. results frame shift mutation introduction stop codon. Translation encoded mRNA would yield prematurely terminated protein. This protein be 1085 amino acids long 73 carboxyl-terminal residues out frame. postulate consequence crossover event between introns resulting nonreciprocal exchange two chromosomes.