Background: Advances in ultrasound technology have revolutionized obstetrical care and have resulted in a greater number of cases of cleft lip with or without cleft palate diagnosed prenatally by ultrasound. This study investigated the experience of receiving a diagnosis of clefting in the prenatal or postnatal period. Methods: Open-ended interviews were conducted with 20 parents of children with cleft lip with or without cleft palate. Of these parents, 12 experienced a prenatal diagnosis of their child's cleft, while eight received the diagnosis at birth. Interviews were transcribed and analyzed using a qualitative description approach with an emphasis on thematic analysis. Common themes emerged from participant's responses to questions regarding the delivery of the diagnosis, preparation for the birth of their child, advantages and disadvantages of prenatal diagnosis, use of the Internet, views on abortion, interaction with other parents, among other issues. Findings: Preliminary findings were synthesized into themes that included "shared parental experiences," "coping," "preparation," "disadvantages," and "alternative perspectives." These overarching themes were divided into subthemes. Advantages cited for prenatal diagnosis included having the time to psychologically adjust to the diagnosis, to become informed, to educate other children, to opt for additional testing, and to plan for the baby's needs. Some participants felt a drawback of prenatal diagnosis was an emotional disruption of the pregnancy, while other participants found no disadvantages. All participants in the prenatal group indicated they were glad they learned of the cleft before the birth of their child. Some participants in the postnatal group would have rather received the diagnosis prenatally, while others were satisfied learning of the diagnosis in the delivery room. Interpretation: There seemed to be greater similarities than differences between the two groups of participants. Parents seemed to be affected more by how the diagnosis was delivered than the timing of the diagnosis. A prenatal diagnosis of a cleft may have a negative impact on the pregnancy, nonetheless parents seemed to want this information. High-resolution ultrasound has become standard of care for many pregnant women. Understanding the consequences of prenatal diagnosis is an important contribution to the field of public health.

Background: Velocardiofacial syndrome (VCFS) is a congenital malformation syndrome with an estimated prevalence of 1:4,000 livebirths. Most cases are caused by a common 3 Mb deletion at 22q11.2. This syndrome exhibits wide inter- and intra-familial variability in phenotypic features including physical, developmental, neurological, and neuropsychiatric manifestations despite the general uniformity in deletion size. The purpose of this meta-analysis was to seek explanations for the differences in the reported prevalence rates of various findings; to more accurately estimate the prevalence of each of the nine traits examined; to provide insight into future research; and to improve the ability for genetic counselors and clinicians to provide more appropriate services and offer appropriate resources. Methods: A PubMed search was performed for keywords associated with VCFS. After an exhaustive search, twenty-nine articles were included. Nine traits of interest were chosen along with five predictor variables. From the articles, prevalence data was abstracted, overall prevalence data was calculated, and unweighted and weighted regression analyses were performed. Results: Ascertainment bias may be associated with the prevalence of ADHD; the prevalence of males does not appear to play a role in the discrepant data; the number of years ago a study was published is associated with prevalence of ADHD, cleft palate, palatal findings and VPI; age range is associated with the prevalence of congenital heart defects; having a de novo deletion is significantly associated with the prevalence of cleft palate and SMCP; and geographical location is significantly associated with the prevalence of palatal anomalies. Overall prevalence rates are as follows: ADHD 17.2%, CHD 73.5%, cleft palate 11.6%, submucosal cleft palate 17.0%, velopharyngeal insufficiency 35.1%, any palatal anomaly 54.1%, any psychiatric disorder 34.4%, schizophrenia 12.6%, and hypotonia 64.5%. Conclusions: Due to small sample sizes, it is difficult to draw conclusions on the presented data; however, this analysis provides useful insight into future avenues of research especially with regards to behavioral and psychiatric illnesses. Many findings, especially psychiatric illnesses, associated with VCFS, pose a significant public health burden thus it would be of public health significance to find answers to some of the questions addressed in this study.

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease affecting approximately one million individuals in the United States. Individuals with lupus are at an extremely increased risk (up to 50-fold) to develop coronary heart disease (CHD) compared to the general population. Traditional risk factors are insufficient to explain the increase in risk. The presence of anti-phospholipid antibodies (seen at a higher rate in SLE patients than in the general population) is suspected to play a role. CHD is the leading cause of death for both men and women of all ethnic groups in the United States. Understanding the genetic causes of CHD in high risk populations, such as individuals with SLE, can help facilitate the understanding of CHD in the general population. Due to the large public health significance of CHD, investigating the contributing factors and disease etiology could have a major impact on risk assessment and possible treatment of CHD. One gene involved in lipid metabolism, a major part of the development of atherosclerotic plaques and CHD, is paraoxonase-1 (PON1). PON1 encodes the enzyme paraoxonase, which inhibits the oxidation of low density lipoprotein (LDL) to help prevent its uptake by macrophages, thereby reducing the incidence of atherosclerotic plaques. Eight genetic variants in the PON1 gene were examined to determine their impact on SLE disease status, the presence of anti-phospholipid antibodies (APA), and PON activity. Polymorphisms in PON1 were not found to have a significant impact on SLE disease status or the presence of APA, however three of the polymorphisms studied were found to have a significant impact on PON activity. While SLE and CHD are complex diseases, likely resulting from gene-gene and gene-environment interactions, the identification of these associations between PON1 polymorphisms and PON activity may help to clarify the role of PON in CHD development and possibly lead to more accurate risk assessment and/or the investigation of treatment options for this common disease.

Systemic Lupus Erythematosus (SLE) is an autoimmune disease that targets the vascular system, and can result in premature atherosclerotic vascular disease. The causes of SLE and many of the SLE associated problems, such as thrombosis, anitphospholipid syndrome, and atherosclerosis, which are significant public health concerns, are thought to be multifactorial, or caused by interactions of many environmental and genetic factors. Several genes have been proposed and studied in conjunction with these manifestations. This study focuses on one of these genes, apolipoprotein H (APOH gene, beta-2-GPI protein). The effects of several polymorphisms within the coding region in the APOH gene have been studied; however, possible effects of the single nucleotide polymorphisms (SNPs) within the promoter region have not been characterized. In this study, 6 SNPs in the APOH promoter were genotyped in 381 SLE women and 497 healthy women controls. This study aimed to determine the association of these polymorphisms with the occurrence of SLE, with the plasma levels of beta-2-GPI, and with the presence of antiphospholipid antibodies (APA). It was hypothesized that the genetic variation in the promoter region of the APOH gene may affect the risk of SLE and may do so through an effect on plasma beta-2-GPI levels or through its influence on APA. Among whites, the risk of SLE was modestly affected by the -1219 SNP (p = 0.057). While in blacks, the -759 SNP (p = 0.022) and the -700 SNP (p = 0.035) showed association with SLE. The haplotype pattern in whites was associated with SLE risk (p = 0.00015). The -643 SNP showed a modest effect on plasma beta-2-GPI levels in white SLE cases (p = 0.096) and black controls (p = 0.081). Significant differences were seen between antibody negative and all antibody positive groups in whites for the -1284 SNP (p = 0.02) and the -759 SNP (p = 0.046). These results suggest that genetic variation in the APOH promoter may affect SLE risk, beta-2-GPI levels, and the occurrence of antiphospholipid antibodies.

Genetic testing for a hereditary breast cancer predisposition has been available since 1996. Since then, many at-risk individuals have pursued testing for a variety of reasons including medical management, surgical decision-making, and family planning. However, as a result of the ability to learn ones cancer risk, women often struggle to incorporate this information into their lives and are faced with complex decision-making. Providing comprehensive services for this population that address these concerns is a matter of public health importance. This study documents the process of designing a support group for women who have tested positive for a hereditary breast cancer predisposition. Thirty-three women who have previously tested positive for mutations in BRCA1, BRCA2, or PTEN were invited to participate in a monthly support/discussion group and were sent questionnaires and informed consent documents for study participation. Nineteen of the thirty-three (57.6%) women responded, five (27.8%) were group participants and fourteen (72.2%) were non-participants. The questionnaire addressed experiences with cancer, management decisions, risk perceptions, existing levels of support, causes of anxiety, and communication with family members. As hypothesized, group participants had higher perceptions of breast cancer risk, lower confidence in medical management decisions, and less support from family and friends than non-participants. In addition, group participants were more likely to be younger, to have received their results 1-2 years ago, to not have a personal history of cancer, and to experience greater overall anxiety. Factors influencing perceived breast cancer risk and the need for support services included the number of first or second degree relatives with breast cancer, whether the relative was deceased or alive, the election of preventative surgery, and the time elapsed since result disclosure. Other findings included correlations between (a) perceived breast cancer risk and both perceived ovarian cancer risk and need for a support group, (b) perceived ovarian cancer risk and anxiety about talking with ones partner, and (c) all items addressing sources of anxiety. This study provides information that can potentially aid public health professionals who work with high-risk women and who are organizing or designing support services for women with a hereditary breast cancer predisposition.

Background: The genetic mechanisms that lead to head and neck squamous cell carcinoma (HNSCC) are incompletely understood. Cancer predisposition is associated with chromosome instability and hypersensitivity to DNA damaging agents. Fanconi anemia patients are extremely sensitive to crosslinking agents and are at increased risk of developing several cancers including leukemias, gynecological, and head and neck cancers. The Fanconi Anemia proteins (FANCs) are involved in pathways necessary for crosslink damage recognition and repair. Eight FANC proteins (A/B/C/F/G/I/J/L) assemble into a nuclear complex and two other proteins, FANCD1/BRCA2 and FANCD2 act downstream of the core complex. This FA protein complex is required for the monoubiquitination of the FANCD2 protein in response to DNA damage. By testing head and neck tumors for FANC characteristics, such as hypersensitivity to DNA crosslinking agents, increased chromosome breakage FANCD2 protein ubiquitination, formation of radial figures and genomic instability, we can determine whether this specific DNA damage repair pathway is intact in the tumors. Methods: Head and neck tumor cell lines were treated with the clastogenic crosslinking agent, diepoxybutane (DEB), and double-strand breaks and chromosomal aberrations were quantified. FANCA and FANCD2 cell lines were analyzed as positive controls and normal peripheral blood lymphocytes were used as negative controls. iv Findings: HNSCC cell lines treated with DEB have an increased number of DEB-induced double-strand breaks compared to normal lymphocytes, as evidenced by increased chromosomal breaks and tri- and quadriradials, suggesting defects in the DNA damage response. Interpretation: Patients who are hypersensitive to DNA damage are at increased risk of developing several types of cancer at an early age. Likewise, we predicted and showed that head and neck tumors have defects in the FANC pathway. This might suggest that the genes in the pathway either had germline or acquired alterations (mutations or regulatory defects), which could be tested by comparing normal cells from these patients to the tumor cells. Identifying and examining the mechanisms by which DNA damage occurs and is repaired can lead to a better understanding of genetic predisposition to cancer and to advances in early detection and treatment, therefore reducing morbidity and mortality. v

The Center for Minority Health (CMH) within the University of Pittsburgh has the mission to eliminate racial health disparities by 2010. One community-based intervention focuses on family health histories. Family health histories, or pedigrees, have been shown to be effective tools for identifying individuals at risk for common diseases who may benefit from increased screening or other risk reduction behaviors. Genetic counseling graduate students provide individuals with information pertaining to the importance of family history information in reducing the risk of chronic disease. Students travel to various locations in the African American community where they collect individuals family health histories. Individuals who participate have the opportunity to enroll in the Minority Research Recruitment Database from which they can be contacted regarding research for which they may qualify. This is the Centers effort to increase minority recruitment. This has public health relevance given that minorities are often under-represented in research and it is thought that increasing minority recruitment will aid in elimination of racial health disparities. This study was developed to characterize individuals who elected to enroll in the database and compare them to those who declined enrollment. Factors for comparison include demographics, recruitment variables, opinions regarding research, health care, personal health, and family history. Factors were assessed for 126 participants of which approximately 80% enrolled in the database and 20% declined. Analysis revealed that those more likely to participate in the database were female, without health insurance, more likely to respond to monetary incentives, more likely to talk to their physician about concerns for developing a disease, and less likely to have previously refused participation in a clinical trial. These results indicate that women are more likely than men to seek health information that pertains to their family history, incentives act as a motivation for individuals to enroll in this database, and issues of distrust may still act as a barrier to research participation for African Americans.

Acute lymphoblastic leukemia (ALL) is the most common malignancy occurring in childhood and accounts for 77% of all leukemia cases. Long-term survival is greater than 80% with appropriate treatment. Chemotherapy is the most widely used treatment, but it can have significant side effects including neutropenia and immunosuppression. Interleukin (IL-10) is an immunoregulatory cytokine with anti-inflammatory effects. It inhibits some cells like macrophages while stimulating other cells like B cells. IL-10 has been found to be involved in conditions involving an immune response and inflammation, including pneumonia, septic shock, and graft versus host disease (GVHD). Myeloperoxidase (MPO), which catalyzes the production of hypochlorite from chlorides and hydrogen peroxide, is an abundantly expressed hemoprotein with anti-microbial effects and a major player in host defense. MPO has been implicated in the pathogenesis of a number of conditions and associated with certain infections. In this study, polymorphisms in MPO and IL-10 were investigated to test their association with risk of infection in a population of Caucasian patients with ALL. Genotyping was performed by enzyme digest for IL-10 polymorphism -592(C/A) and by pyrosequencing for the MPO polymorphisms -129(G/A) and -463(G/A). Allele frequencies at each site were in Hardy Weinberg Equilibrium (HWE). No significant correlation was found between the genotype at IL-10 -592, MPO -129 or MPO -643 and infection episodes in our patient population. As the study population was relatively small, no strong conclusions can be drawn, but implications for further research can be identified. Public Health Significance: Knowledge of the effects of certain genetic polymorphisms may be important when treating patients with ALL. Patients at increased risk of infection may require prophylaxis or more intense surveillance to ensure a better outcome.

Sickle cell trait carriers are healthy; however, they are at risk to have children with sickle cell disease (SCD), a serious hematologic disorder. Unsuccessful population screening for sickle cell trait (SCT) has resulted in a large population of African American individuals entering childbearing age with no knowledge of their risk. Recent experience with newborn screening follow-up of hemoglobinopathies has shown that interest in genetic screening for SCT is low. This study aims to understand and increase the level of acceptance of genetic screening among the African American population through a program of education and assessment of the current state of SCD cultural health beliefs. This is important for Public Health because SCD is the most common genetic disorder affecting the African American community and education to promote screening must be sensitive to the cultural beliefs of the community. Utilizing a method of anonymous surveys given to female African American patients within a busy prenatal clinic the effect of education of SCD on the acceptance of genetic screening for SCT has been assessed. The Health Belief Model was used to assess the current state of health beliefs regarding SCD and trait testing through anonymous surveys. This study revealed that a brief educational intervention regarding SCD in a prenatal setting is effective in significantly increasing knowledge of SCD and acceptance of screening for SCT (p-value < 0.001). African American women of childbearing age have a high perception of severity of SCD, a low perception of susceptibility to SCD, a high perception of benefit to SCT testing and a low perception of barriers to testing for SCT. Education within a prenatal setting can be used as a model to increase acceptance of screening for SCT. A high level of knowledge of SCD is associated with a high level of acceptance; however, the Health Belief Model revealed that currently the majority of the participants do not feel that they are personally at risk to have a child with SCD, regardless of SCD knowledge. Future education of SCD must take into account these beliefs in order to effectively motivate interest in SCT testing.

Prenatally detected chromosomal mosaicism complicates genetic counseling as there is variability in phenotypic outcome and available information pertaining to phenotypic consequences is limited. The objective of this study was to identify the phenotypic effects of mosaicism that was diagnosed prenatally. A total of 4,599 CVS specimens and 15,688 amniocentesis specimens were collected between 1991 and 2005 and clinical information was reviewed for all mosaic cases. Of those procedures, 76 CVS specimens (1.65%) and 66 amniocentesis specimens (0.42%) indicated a mosaic result. However, seven of the mosaic amniocentesis results were observed after a previous mosaic CVS result. When these specimens were removed from the calculation, the incidence of mosaic amniocenteses was 0.38%. Of the cases that had follow-up cytogenetic testing, CVS cases were found to have a true mosaicism rate of 23.6% while amniocentesis cases had a rate of 60.7%. The rates of prenatally detected mosaicism and true fetal mosaicism for Magee-Womens Hospital are comparable to the rates reported in literature. This study found mosaic results involving trisomy for chromosomes 2, 7, 8, 9, 10, 12, 13, 15, 16, 18, 20, 21, 22, X, and Y. In addition, there was monosomy for chromosomes 21, 22, and X, tetraploidy, structural aberrations, and supernumerary marker chromosomes. However, no cases of UPD were identified. From this information, associations were made between the phenotypic outcomes observed in this study and those reported from previous studies. Based on the information provided from this study, it is apparent that phenotype can vary, even when the same abnormality is involved and that more information is needed regarding long term consequences of prenatally diagnosed mosaicism. The results of this study are important to public health because it provides additional data regarding the phenotypic results after prenatal diagnosis of mosaicism for various chromosome abnormalities and increases the understanding of the role of mosaicism in prenatal diagnosis, enabling more effective patient counseling.