More information on how we inherit hypercholesterolemia

"Familial hypercholesterolemia (FH) is characterized by increased levels of plasma LDL cholesterol that leads to the formation of tendon xanthomas, accelerated atherosclerosis, and premature coronary heart disease. In most cases, FH is an autosomal dominant disorder caused by mutations in the LDL receptor gene that lead to defective clearance of plasma LDL. There is a strong gene-dosage effect, and homozygous FH patients exhibit a severe and highly characteristic clinical phenotype."1The investigators have previously described two families with autosomal recessive hypercholesterolemia that was not due to mutations in the LDL receptor gene but was characterized by defective LDL receptor-dependent internalisation and degradation of LDL by transformed lymphocytes from the patients. The defective gene was mapped to chromosome 1p36 showing that the disorder in these and a third English family was due to novel mutations in ARH1, a newly identified gene encoding an adaptor-like protein. Cultured skin fibroblasts from affected individuals exhibit normal LDL receptor activity, but their monocyte-derived macrophages are similar to transformed lymphocytes, being unable to internalise and degrade LDL. Retroviral expression of normal human ARH1 restored LDL receptor internalisation in transformed lymphocytes from an affected individual, as demonstrated by uptake and degradation of 125I-labelled LDL and confocal microscopy of cells labelled with anti-LDL-receptor Ab.Link below for full storyReference...