Molecular diagnosis of hereditary cystatin C amyloid angiopathy

• Published in: Biochemical Medicine and Metabolic Biology
• Main Authors: Jonsdottir, S, Palsdottir, A
• Other Authors: Department of Medical Genetics, Blood Bank, National University Hospital, Reykjavik, Iceland.
• Format: Article in Journal/Newspaper
• Language: English
• Published: Academic Press 2011
• Subjects: Amino Acid Sequence; Amyloidosis; Base Sequence; Cerebral Hemorrhage; Cystatin C; Cystatins; Humans; Iceland; Molecular Sequence Data; Point Mutation; Polymorphism; Restriction Fragment Length
• Online Access: http://hdl.handle.net/2336/122645; https://doi.org/10.1006/bmmb.1993.1014

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field 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.