title: Molecular diagnosis of hereditary cystatin C amyloid angiopathy.
abstract: Hereditary cystatin C amyloid angiopathy (HCCAA) is an autosomal dominant disorder characterized by the deposition of amyloid in most investigated tissues. The main component of the amyloid deposits is a variant of the cysteine proteinase inhibitor cystatin C, and the most serious consequence of the disease is that amyloid deposition in the cerebral arteries leads to a massive brain hemorrhage and death before 40 years of age. HCCAA has been shown to be caused by a T-->A point mutation in the codon for leucine at position 68 in exon 2 of the cystatin C gene, which results in a leucine-->glutamine amino acid substitution in the cystatin C molecule. Since the HCCAA-causing mutation abolishes an AluI restriction site in the cystatin C gene, analysis of this AluI restriction fragment-length polymorphism (RFLP) enables simple and accurate molecular diagnosis of HCCAA. One hundred ninety-one individuals have now been screened for the HCCAA causing mutation, including a fetus for prenatal diagnosis. Thirty-six individuals belonging to nine Icelandic families have been found to have the mutation and it is highly probable that these families descend from a common ancestor.
authors.affiliation: Department of Medical Genetics, Blood Bank, National University Hospital, Reykjavik, Iceland.
authors.forename: S
authors.initials: S
authors.lastname: Jonsdottir
authors.forename: A
authors.initials: A
authors.lastname: Palsdottir
mesh_terms: D000595:Amino Acid Sequence; D000686:Amyloidosis / Q000235:genetics*; D001483:Base Sequence; D002543:Cerebral Hemorrhage / Q000235:genetics*; D055316:Cystatin C; D015891:Cystatins / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D007055:Iceland; D008969:Molecular Sequence Data; D017354:Point Mutation; D012150:Polymorphism, Restriction Fragment Length
chemical_list: C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins