Hereditary cystatin C amyloid angiopathy: Identification of the disease causing mutation and specific diagnosis by polymerase chain reaction based analysis

Summary, in English

Hereditary cystatin C amyloid angiopathy (HCCAA) is a dominantly inherited disease characterized by amyloidosis, dementia and fatal cerebral hemorrhage of young adults. A method for rapid and simple diagnosis of HCCAA is described. It is based upon oligonucleotide-directed enzymatic amplification of a 275-bp genomic DNA segment containing exon 2 of the cystatin C gene from a blood sample, followed by digestion of the amplification product with AluI. Loss of an AluI recognition site in the amplified DNA segment from HCCAA patients results in a deviating band-pattern at agarose gel electrophoresis, compared with that obtained from normal subjects or unaffected HCCAA family members. In a population of 9 patients with manifest HCCAA, 14 patients with other causes of brain hemorrhage and 16 healthy individuals, the diagnostic procedure displayed a sensitivity and specificity for HCCAA of 100%. Amplified DNA segments from 4 HCCAA patients of four different families were analyzed by nucleotide sequencing; the HCCAA-causing mutation in all families was found to be a single TrarrA substitution in the codon for amino acid residue 68 of cystatin C.

• Author: Magnus Abrahamson; S Jonsdottir; I Olafsson; O Jensson; Anders Grubb
• Department/s: Division of Clinical Chemistry and Pharmacology
• Publishing year: 1992
• Language: English
• Pages: 377-380
• Publication/Series: Human Genetics
• Volume: 89
• Issue: 4
• Links: http://dx.doi.org/10.1007/BF00194306
• Document type: Journal article
• Publisher: Springer
• Topic: Medical Genetics
• Status: Published
• ISBN/ISSN/Other: ISSN: 1432-1203