Studies on the Cystatin C Gene in Patients with Hereditary Cystatin C Amyloid Angiopathy (HCCAA) with Cerebral Haemorrhage
Hereditary cystatin C amyloid angiopathy is a dominant disorder caused by the deposition of cystatin C in the brain arteries or arterioles of patients, leading to strokes at an early age.
The cystatin C gene in HCCAA patients was analysed to establish whether a marker for the disease could be found. A search for restriction fragment length polymorphism (RFLP) revealed a Sac I RFLP close to the 3′ end of the gene. The polymorphic fragments of 3.0 kb and 8.6 kb showed no correlation with the disease.
A DNA hybridization analysis was also performed on a reported Leu→Gln amino acid substitution in the amyloid cystatin C (1) using two allele-specific oligonucleotide probes corresponding to the normal leucine codon CTG (2) and the glutamine codon CAG. The oligonucleotide probes were hybridized to DNA sequences enzymatically amplified with cystatin C specific primers located on both sides of the reported mutation. The oligonucleotide probe corresponding to the normal sequence hybridized to all DNA samples, both from patients and healthy controls, while no hybridization signal was seen with the “mutant” probe.
The results suggest that the cystatin C gene is not closely linked to the gene causing the disease.
KeywordsRestriction Fragment Length Polymorphism Oligonucleotide Probe Amyloid Fibril Healthy Control Individual Human Insulin Gene
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