Pedigrees are a foundation of genetic counseling and human genetic research. To protect patient/subject and family privacy and confidentiality it is not unusual to find published pedigrees that have been masked (i.e. a pedigree that has been changed in ways that are obvious to the reader such as diamonds to mask gender) or altered (i.e. changing pedigree information in ways that are not obvious to the reader such as changing gender and birth order or deleting unaffected siblings from the pedigree). Failure to report pedigree data (e.g. omitting ages, ethnicity, etc.) is another measure used to protect subject and family confidentiality. At what point do such practices hinder the recognition of genetic processes? Is there evidence that harm has occurred to subjects who have appeared in published pedigrees? How does the researcher or clinician determine which information is essential to record on the pedigree? The author uses a historical perspective and case examples to illustrate the issues of balancing protection of the genetic subject's privacy with the reporting of unaltered family data. The author presents several critical questions for peer reviewers and investigators to consider when a pedigree is included in a manuscript, or for researchers involved in family studies.
Congenital dysfibrinogenemia is a rare cause of unexplained thrombosis. However, most individuals with dysfibrinogenemia are asymptomatic, suggesting that co-morbid factors contribute to thrombo-embolic events. The potential roles of additional genetic or acquired prothrombotic risk factors are poorly understood because detailed family studies are lacking. Herein, we describe a family whose propositus was a young Caucasian man with recurrent venous thrombo-emboli and dysfibrinogenemia due to heterozygosity for an Arg→Cys substitution at residue 275 in the-chain. The only additional thrombophilic abnormality found in the proband was heterozygosity for a G/A transition at position −455 in the fibrinogen-chain promoter; a genotype associated with high acute phase levels of fibrinogen. The proband's father, who died of a cerebral artery thrombosis, carried the R275C substitution but not the-promoter −455 variant. Among 14 living relatives, eight were heterozygous for one or the other mutation and only one, a 21-year-old niece, was dually affected. None had suffered bleeding or thrombosis. In vitro studies of the pro-band's purified fibrinogen revealed markedly abnormal thrombin-catalyzed polymeriza-tion and delayed fibrin clot lysis by tPA-activated plasmin. We hypothesize that the R275C substitution predisposes to thrombosis by generating clots that are relatively resistant to fibrinolysis. The clinical risk is low, however, in the absence of an additional thrombophilic mutation. The-promoter variant could, theoretically, contribute to this risk by augmenting expression of the dysfibrinogen under conditions of stress. Like the common hereditary thrombophilias, heterozygous familial dysfibrinogenemia induces thrombosis in the setting of multiple prothrombotic influences. Am. J. Hematol. 64:242-250, 2000.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.