A screen of 38 unrelated hypocholesterolemic subjects as well as 25 unrelated familial hypocholesterolemia cases that responded well to statin therapy (63 total) found this variant in one of the first set of unrelated hypocholesterolemic subjects. A total of nine individuals were found to have missense variants in this gene. As controls they sequenced 441 hypercholesterolemic subjects that lacked mutations in LDLR and apolipoprotein B-100 and found none of them had these variants.
(Note, *hypo*cholesterolemia, not hyper.)
case+: 1, case-: 62
control+: 0, control-: 441
This gives p=0.12 using a two-tailed fisher’s exact test.
A pedigree is given for the family of this proband and shows no individuals with hypocholesterolemia that do not have the variant, but only 2/5 carriers have hypocholesterolemia (<2.5 percentile) — segregation is not inconsistent, but penetrance is implied to be low (40%) and not a significant LOD score.