Carney complex (CNC) is a familial multiple neoplasia syndrome characterized by cardiac and extracardiac myxomas in the setting of spotty skin pigmentation and endocrinopathy. We previously identified
PRKAR1A
(regulatory subunit 1α of protein kinase A) mutations in CNC. Mutational analyses of the
PRKAR1A
gene in 51 unrelated CNC probands now detect mutations in 65%. All mutations, except for one unique missense mutation, lead to
PRKAR1A
haploinsufficiency. Therefore, we studied the consequences of
prkar1a
haploinsufficiency in mice. Although we did not observe cardiac myxomas or altered pigmentation in
prkar1a
+/–
mice, we did observe some phenotypes similar to CNC, including altered heart rate variability. Moreover,
prkar1a
+/–
mice exhibited a marked propensity for extracardiac tumorigenesis. They developed sarcomas and hepatocellular carcinomas. Sarcomas were frequently associated with myxomatous differentiation. Tumors from
prkar1a
+/–
mice did not exhibit
prkar1a
loss of heterozygosity. Thus, we conclude that although PRKAR1A haploinsufficiency does predispose to tumorigenesis, distinct secondary genetic events are required for tumor formation.
This review provides a guide to researchers who wish to establish a biobank. It also gives practical advice to investigators seeking access to samples of healthy or diseased human hearts. We begin with a brief history of the Sydney Heart Bank (SHB) from when it began in 1989, including the pivotal role played by the late Victor Chang. We discuss our standard operating procedures for tissue collection which include cryopreservation and the quality assurance needed to maintain the long-term molecular and cellular integrity of the samples. The SHB now contains about 16,000 heart samples derived from over 450 patients who underwent isotopic heart transplant procedures and from over 100 healthy organ donors. These enable us to provide samples from a wide range of categories of heart failure. So far, we have delivered heart samples to more than 50 laboratories over two decades, and we answer their most frequently asked questions. Other SHB services include the development of tissue microarrays (TMA). These enable end users to perform preliminary examinations of the expression and localisation of target molecules in diseased or aging donor hearts, all in a single section of the TMA. Finally, the processes involved in managing tissue requests from external users and logistics considerations for the shipment of human tissue are discussed in detail.
Late-onset AV block occurs in 2.4% of patients with orthotopic heart transplant or heart-lung transplant. AV block is predominantly intermittent and, often, does not progress to permanent AV block. There are no predictable factors for its onset.
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.