title: A "de novo" mutation of the LDL-receptor gene as the cause of familial hypercholesterolemia.
abstract: Familial hypercholesterolemia (FH) is a common genetic disorder caused by mutations of the LDL-receptor gene and transmitted as a co-dominant trait. However, there are some forms of hypercholesterolemia which have a recessive type of transmission. We have identified a subject with the clinical phenotype of heterozygous FH whose parents had normal plasma lipid values, suggesting a recessive type of transmission. The analysis of the LDL-receptor gene revealed that the patient was heterozygous for a G>C transversion in exon 4, which results in a serine for cysteine substitution at position 88 (C88S) of the receptor protein. Since this novel mutation was not found in the proband's parents and non-paternity was excluded, we concluded that the patient was a carrier of a "de novo" mutation. Haplotype analysis of LDL-receptor locus indicated that this "de novo" mutation occurred in the paternal germ line. The C88S mutation is the likely cause of LDL-receptor defect as it was present in the proband's hypercholesterolemic son and was not found in 200 chromosomes of control subjects.
authors: Department of Internal Medicine, University of Genoa, Viale Benedetto XV, 6 16132, Italy.
authors: Livia
authors: L
authors: Pisciotta
authors: Alfredo
authors: A
authors: Cantafora
authors: Francesco
authors: F
authors: De Stefano
authors: Silvia
authors: S
authors: Langheim
authors: Sebastiano
authors: S
authors: Calandra
authors: Stefano
authors: S
authors: Bertolini
mesh_terms: D002648:Child; D003545:Cysteine / Q000737:chemistry; D006579:Heterozygote; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010334:Paternity; D010375:Pedigree; D011973:Receptors, LDL / Q000737:chemistry / Q000235:genetics*; D012694:Serine / Q000737:chemistry
chemical_list: D011973:Receptors, LDL; D012694:Serine; D003545:Cysteine