Abstract null null Heterozygous (carrier) status for an autosomal recessive condition is traditionally considered to lack significance for an individual's health, but this assumption has been challenged by a growing body of evidence. Carriers of several autosomal recessive disorders and some X-linked diseases are potentially at risk for the pathology manifest in homozygotes. This minireview provides an overview of the literature regarding health risks to carriers of two common autosomal recessive conditions on the Recommended Uniform Screening Panel: sickle cell disease [sickle cell trait (SCT)] and cystic fibrosis (CF). We also consider and comment on bioethical and policy implications for newborn blood screening (NBS). Health risks for heterozygotes, while relatively low for individuals, are often influenced by intrinsic (e.g., other genomic variants or co-morbidities) and extrinsic (environmental) factors, which present opportunities for personalized genomic medicine and risk counseling. They create a special challenge, however, for developing screening/follow-up policies and for genetic counseling, particularly after identification and reporting of heterozygote status through NBS. Although more research is needed, this minireview of the SCT and CF literature to date leads us to propose that blanket terms such as “healthy heterozygotes” or “unaffected carriers” should be superseded in communications about NBS results, in favor of a more nuanced paradigm of setting expectations for health outcomes with “genotype-to-risk.” In the molecular era of NBS, it remains clear that public health needs to become better prepared for the full range of applied genetics.
Objective null To explore primary care providers’ (PCPs’) preferred roles and confidence in caring for infants receiving a positive cystic fibrosis (CF) newborn screening (NBS) result, as well as management of CF family planning issues, given that expanded NBS has resulted in an increase in positive results. null Design null Mailed questionnaire. null Setting null Ontario. null Participants null Ontario FPs, pediatricians, and midwives identified by Newborn Screening Ontario as having had an inf...
#8Adolfo Correa(UMMC: University of Mississippi Medical Center)
Soluble urokinase plasminogen activator receptor (suPAR) is the circulating form of urokinase plasminogen activator receptor, a glycosyl-phosphatidylinositol–anchored membrane protein expressed in various cell types including kidney podocytes and endothelial cells ([1][1]). suPAR has been
PURPOSE Congenital primary hypothyroidism (CH) is a state of inadequate thyroid hormone production detected at birth, caused either by absent, underdeveloped or ectopic thyroid gland (dysgenesis), or by defected thyroid hormone biosynthesis (dyshormonogenesis). A genetic component has been identified in many cases of CH. This review summarizes the clinical and biochemical features of the genetic causes of primary CH. METHODS A literature review was conducted of gene defects causing congenital hy...
Importance The incidence of and mortality from coronary heart disease (CHD) are substantially higher among African American individuals compared with non-Hispanic White individuals, even after adjusting for traditional factors associated with CHD. The unexplained excess risk might be due to genetic factors related to African ancestry that are associated with a higher risk of CHD, such as the heterozygous state for the sickle cell variant or sickle cell trait (SCT). Objective To evaluate whether ...
#1Tamara S. Roman(UNC: University of North Carolina at Chapel Hill)H-Index: 5
#2Stephanie B. Crowley(UNC: University of North Carolina at Chapel Hill)H-Index: 3
Last. Jonathan S. Berg(UNC: University of North Carolina at Chapel Hill)H-Index: 52
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Summary Newborn screening (NBS) was established as a public health program in the 1960s and is crucial for facilitating detection of certain medical conditions in which early intervention can prevent serious, life-threatening health problems. Genomic sequencing can potentially expand the screening for rare hereditary disorders, but many questions surround its possible use for this purpose. We examined the use of exome sequencing (ES) for NBS in the North Carolina Newborn Exome Sequencing for Uni...
#2Alexandra Sims(GW: George Washington University)H-Index: 3
Last. Philip M. Farrell(UW: University of Wisconsin-Madison)H-Index: 80
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Objectives To measure parental perceptions of child vulnerability, as a precursor to developing a population-scale mechanism to mitigate harm after newborn screening. Study design Participants were parents of infants aged 2-5 months. Parental perceptions of child vulnerability were assessed with an adapted version of the Vulnerable Baby Scale. The scale was included in the script for a larger study of telephone follow-up for 2 newborn blood screening samples (carrier status for cystic fibrosis o...
Last. Philip M. Farrell(UW: University of Wisconsin-Madison)H-Index: 80
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Objective To conduct interviews with a multiyear sample of parents of infants found to have heterozygous status for sickle cell hemoglobinopathy or cystic fibrosis during newborn blood screening (NBS). Study design Interviewers with clinical backgrounds telephoned parents, and followed a structured script that blended follow-up and research purposes. Recruiting followed several steps to minimize recruiting bias as much as possible for a NBS study. Results Follow-up calls were conducted with pare...
The role of X-inactivation is often ignored as a prime cause of sex differences in disease. Yet, the way males and females express their X-linked genes has a major role in the dissimilar phenotypes that underlie many rare and common disorders, such as intellectual deficiency, epilepsy, congenital abnormalities, and diseases of the heart, blood, skin, muscle, and bones. Summarized here are many examples of the different presentations in males and females. Other data include reasons why women are ...
BACKGROUND: Sickle cell trait (SCT) has been associated with an increased risk of sudden death in athletes during strenuous exercise. In August 2010, the National Collegiate Athletic Association (NCAA) began requiring athletes to be screened for SCT, provide proof of SCT status, or sign a waiver and launched an educational campaign for athletes, coaches, and medical staff. The impact of this program is unknown. The purpose of this study was to determine the incidence of death associated with sic...
#2Michael J. Rock(UW: University of Wisconsin-Madison)H-Index: 31
Last. Mei W. Baker(UW: University of Wisconsin-Madison)H-Index: 17
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Discovery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene was the long-awaited scientific advance that dramatically improved the diagnosis and treatment of cystic fibrosis (CF). The combination of a first-tier biomarker, immunoreactive trypsinogen (IRT), and, if high, DNA analysis for CF-causing variants, has enabled regions where CF is prevalent to screen neonates and achieve diagnoses within 1–2 weeks of birth when most patients are asymptomatic. In addition, IRT/DNA (CF...
