ArticlePLoS genetics2008
A drastic reduction in the life span of cystatin C L68Q carriers due to life-style changes during the last two centuries.
Article in PLoS genetics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 33 citations in OpenAlex.
- Basement membrane remodeling with fibroblast activation and cystatin C aggregation in cerebral vessels of hereditary cystatin C amyloid angiopathy.Acta neuropathologica communications · 2026Article
- Clinical Management of Cerebral Amyloid Angiopathy.Journal of clinical medicine · 2025Review
- The historical background of hereditary cystatin C amyloid angiopathy: Genealogical, pathological, and clinical manifestations.Brain pathology (Zurich, Switzerland) · 2025Review
- Parental Influence on Intracerebral Hemorrhage Onset in Hereditary Dutch-Type Cerebral Amyloid Angiopathy.Cerebrovascular diseases (Basel, Switzerland) · 2025Article
- Clinical considerations in early-onset cerebral amyloid angiopathy.Brain : a journal of neurology · 2023Review
- NAC blocks Cystatin C amyloid complex aggregation in a cell system and in skin of HCCAA patients.Nature communications · 2021Article
- Finnish gelsolin amyloidosis causes significant disease burden but does not affect survival: FIN-GAR phase II study.Orphanet journal of rare diseases · 2020Article
- Entering the post-epigenomic age: back to epigenetics.Open biology · 2018Article
- Pathological changes in basement membranes and dermal connective tissue of skin from patients with hereditary cystatin C amyloid angiopathy.Laboratory investigation; a journal of technical methods and pathology · 2017Article
- Evidence of Alternative Cystatin C Signal Sequence Cleavage Which Is Influenced by the A25T Polymorphism.PloS one · 2016Article
- Developmental regulation of synthesis and dimerization of the amyloidogenic protease inhibitor cystatin C in the hematopoietic system.The Journal of biological chemistry · 2014Article
- Iceland-genetic counseling services.Journal of genetic counseling · 2013Article
- Male and female differential reproductive rate could explain parental transmission asymmetry of mutation origin in Hirschsprung disease.European journal of human genetics : EJHG · 2012Article
- Review
- Schizophrenia and vitamin D related genes could have been subject to latitude-driven adaptation.BMC evolutionary biology · 2010Article
- Is type 2 diabetes an amyloidosis and does it really matter (to patients)?Diabetologia · 2010Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hereditary cystatin C amyloid angiopathy (HCCAA) is an autosomal dominant disease with high penetrance, manifest by brain hemorrhages in young normotensive adults. In Iceland, this condition is caused by the L68Q mutation in the cystatin C gene, with contemporary carriers reaching an average age of only 30 years. Here, we report, based both on linkage disequilibrium and genealogical evidence, that all known copies of this mutation derive from a common ancestor born roughly 18 generations ago. Intriguingly, the genealogies reveal that obligate L68Q carriers born 1825 to 1900 experienced a drastic reduction in life span, from 65 years to the present-day average. At the same time, a parent-of-origin effect emerged, whereby maternal inheritance of the mutation was associated with a 9 year reduction in life span relative to paternal inheritance. As these trends can be observed in several different extended families, many generations after the mutational event, it seems likely that some environmental factor is responsible, perhaps linked to radical changes in the life-style of Icelanders during this period. A mutation with such radically different phenotypic effects in reaction to normal variation in human life-style not only opens the possibility of preventive strategies for HCCAA, but it may also provide novel insights into the complex relationship between genotype and environment in human disease.
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