This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
RAP1B is a RAS-superfamily small GTP-binding protein involved in numerous cell processes. Pathogenic gain-of-function variants in this gene have been associated with RAP1B-related syndromic thrombocytopenia, an ultrarare disorder characterized by hematologic abnormalities, neurodevelopmental delays, growth delay, and congenital birth defects including cardiovascular, genitourinary, neurologic, and skeletal systems. We report a 23-year-old male with a novel, de novo RAP1B gain-of-function variant identified on genome sequencing. This is the third reported case which expands the molecular and phenotypic spectrum of RAP1B-related syndromic thrombocytopenia.
Familial hypercholesterolemia (FH) is a genetic condition which causes elevated low-density lipoprotein cholesterol from birth. With a prevalence of 1 in 250 and the availability of effective treatments, the diagnostic rate of <1 to 10% is unacceptably low. Screening for FH is supported by multiple organizations, but it has not been broadly adopted and implemented across the USA. To investigate the implementation of FH screening, key informants were recruited from across the USA for their expertise in FH-related literature, guidelines, public health, and/or advocacy to complete semistructured interviews guided by implementation science (RE-AIM framework). Sixteen semistructured interviews were analyzed with directed content and thematic analyses, yielding specific barriers and recommendations to improve FH screening. Barriers to FH screening included patient recruitment and participation, equitable access to healthcare, provider discomfort with screening and treating FH, provider burden, lack of public health and legislative support, FH awareness, guideline complexity, facilitation of genetic testing and cascade screening, and lack of coordination between stakeholders. Awareness, engagement, communication, and collaboration between stakeholders is integral to successful FH screening. Individualized plans will be required at national, regional, and institutional levels. FH screening implementation can be achieved through practice facilitation, streamlined screening approaches, electric medical record tools, and consensus guidelines to increase screening adoption and consistent delivery. Reliable funding and established lines of communication between stakeholders can maintain efforts as FH screening progresses.
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.