Ingeborg Rasing, Lisa Jellema, Sabine Voigt, Kanishk Kaushik, Emma A Koemans, Erik W van Zwet, Ellis S van Etten, Steven M Greenberg, Marianne A A van Walderveen, Gisela M Terwindt, Marieke J H Wermer
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引用次数: 0
Abstract
Introduction: Dutch-type cerebral amyloid angiopathy (D-CAA) is an autosomal dominant hereditary form of CAA causing intracerebral hemorrhage (ICH) and cognitive decline. The age of onset of ICH in D-CAA mutation carriers is strikingly variable and ranges from late thirties up to 70 years. We investigated the presence of genetic anticipation and assessed the influence of parental age at onset and sex on age of ICH onset in offspring.
Methods: We included (potential) D-CAA mutation carriers from our prospective D-CAA family database. Participants were sent a questionnaire by mail and asked for the onset age of symptomatic ICH and the onset age of symptomatic ICH of their affected first-degree relative(s), their siblings and affected parent. We used a Cox regression model with the age of onset of the parent as the covariate and the sex of the offspring as the factor. Next, we replaced the sex of the offspring with a factor with four levels: mother/daughter, mother/son, father/daughter, and father/son. We used a random effect per household.
Results: A total of 66 respondents completed the questionnaire. Reported mean age of first symptomatic ICH was similar (both 52 years, p = 0.87) for D-CAA parents (n = 60) and their offspring (n = 100). Offspring with a mother with D-CAA seemed to have an earlier ICH onset (50 years, standard deviation [SD] ± 7) than offspring with a paternal inheritance (54 years, SD ± 6, p = 0.03). There was no association between onset of first ICH of the parent and offspring after adding sex of the offspring to the Cox regression model: hazard ratio 0.99, 95% CI: 0.94-1.03, p = 0.51. The interaction between parent's sex and child's sex was not significant (p = 0.70). The results with and without random effect were essentially identical.
Conclusion: We found no indication for genetic anticipation in D-CAA in general, although maternal inheritance seemed to be associated with an earlier ICH onset.
期刊介绍：
A rapidly-growing field, stroke and cerebrovascular research is unique in that it involves a variety of specialties such as neurology, internal medicine, surgery, radiology, epidemiology, cardiology, hematology, psychology and rehabilitation. ''Cerebrovascular Diseases'' is an international forum which meets the growing need for sophisticated, up-to-date scientific information on clinical data, diagnostic testing, and therapeutic issues, dealing with all aspects of stroke and cerebrovascular diseases. It contains original contributions, reviews of selected topics and clinical investigative studies, recent meeting reports and work-in-progress as well as discussions on controversial issues. All aspects related to clinical advances are considered, while purely experimental work appears if directly relevant to clinical issues.
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