Donor splice mutation (665 + 1 G_T) in familial hypobetalipoproteinemia with no detectable apoB truncation.

We report a 49-member four-generation kindred in which 11 members express familial hypobetalipoproteinemia (FHBL). In other kindreds, various truncated apoB species cosegregate with the FHBL phenotype. In contrast, no truncated apoB proteins were found by immunoblotting of plasma samples in this kindred. Previous linkage analysis showed strong linkage of FHBL to apoB markers. Nucleotide sequence analysis demonstrated a 665 + 1 G_T transition in the splice donor site of intron 5. This probably alters the accuracy and efficiency of mRNA splicing leading to the extremely low apoB levels in plasma. In addition, we detected four novel polymorphisms in the apoB gene.