A "de novo" mutation of the LDL-receptor gene as the cause of familial hypercholesterolemia |
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Authors: | Pisciotta Livia Cantafora Alfredo De Stefano Francesco Langheim Silvia Calandra Sebastiano Bertolini Stefano |
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Institution: | Department of Internal Medicine, University of Genoa, Viale Benedetto XV, 6 16132, Italy. |
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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. |
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