Showing papers by "Saint Francis University published in 2008"

Coronary calcium as a predictor of coronary events in four racial or ethnic groups.

Abstract: BACKGROUND In white populations, computed tomographic measurements of coronary-artery calcium predict coronary heart disease independently of traditional coronary risk factors. However, it is not known whether coronary-artery calcium predicts coronary heart disease in other racial or ethnic groups. METHODS We collected data on risk factors and performed scanning for coronary calcium in a population-based sample of 6722 men and women, of whom 38.6% were white, 27.6% were black, 21.9% were Hispanic, and 11.9% were Chinese. The study subjects had no clinical cardiovascular disease at entry and were followed for a median of 3.8 years. RESULTS There were 162 coronary events, of which 89 were major events (myocardial infarction or death from coronary heart disease). In comparison with participants with no coronary calcium, the adjusted risk of a coronary event was increased by a factor of 7.73 among participants with coronary calcium scores between 101 and 300 and by a factor of 9.67 among participants with scores above 300 (P<0.001 for both comparisons). Among the four racial and ethnic groups, a doubling of the calcium score increased the risk of a major coronary event by 15 to 35% and the risk of any coronary event by 18 to 39%. The areas under the receiver-operating-characteristic curves for the prediction of both major coronary events and any coronary event were higher when the calcium score was added to the standard risk factors. CONCLUSIONS The coronary calcium score is a strong predictor of incident coronary heart disease and provides predictive information beyond that provided by standard risk factors in four major racial and ethnic groups in the United States. No major differences among racial and ethnic groups in the predictive value of calcium scores were detected.

A soluble activin Type IIA receptor induces bone formation and improves skeletal integrity

Abstract: Diseases that affect the regulation of bone turnover can lead to skeletal fragility and increased fracture risk. Members of the TGF-β superfamily have been shown to be involved in the regulation of bone mass. Activin A, a TGF-β signaling ligand, is present at high levels in bone and may play a role in the regulation of bone metabolism. Here we demonstrate that pharmacological blockade of ligand signaling through the high affinity receptor for activin, type II activin receptor (ActRIIA), by administration of the soluble extracellular domain of ActRIIA fused to a murine IgG2a-Fc, increases bone formation, bone mass, and bone strength in normal mice and in ovariectomized mice with established bone loss. These observations support the development of this pharmacological strategy for the treatment of diseases with skeletal fragility.

Notch Inhibits Osteoblast Differentiation And Causes Osteopenia

Abstract: Notch receptors are determinants of cell fate decisions. To define the role of Notch in the adult skeleton, we created transgenic mice overexpressing the Notch intracellular domain(NICD)underthecontrolofthetypeIcollagenpromoter. First-generationtransgenicsweresmallandosteopenic.Bone histomorphometry revealed that NICD caused a decrease in bone volume, secondary to a reduction in trabecular number; osteoblast and osteoclast number were decreased. Low fertility of founder mice and lethality of young pups did not allow the complete establishment of transgenic lines. To characterize the effect of Notch overexpression in vitro, NICD was induced in osteoblasts and stromal cells from Rosa notch mice, in which a STOP cassette flanked by lox P sites is upstream of NICD, by transduction with an adenoviral vector expressing Cre recombinase (Cre) under the control of the cytomegalovirus (CMV) promoter (Ad-CMV-Cre). NICD impaired osteoblastogenesis and inhibited Wnt/-catenin signaling. To determine the effects of notch1 deletion in vivo, mice in which notch1 was flanked bylox P sequences (notch1 loxP/loxP ) were mated with mice expressing Cre recombinase under the control of the osteocalcin promoter. Conditional null notch1 mice had no obvious skeletal phenotype, possibly because of rescue by notch2; however, 1-month-old females exhibited a modest increase in osteoclast surface and eroded surface. Osteoblasts from notch1 loxP/loxP mice, transduced with Ad-CMV-Cre and transfected with Notch2 small interfering RNA, displayed increased alkaline phosphatase activity. In conclusion, Notch signaling in osteoblasts causes osteopenia and impairs osteoblastogenesis by inhibiting the Wnt/-catenin pathway. (Endocrinology 149: 3890–3899, 2008)

A soluble activin Type IIA receptor induces bone formation and improves skeletal integrity

Abstract: Diseases that affect the regulation of bone turnover can lead to skeletal fragility and increased fracture risk. Members of the TGF-superfamily have been shown to be involved in the regulation of bone mass. Activin A, a TGF-� signaling ligand, is present at high levels in bone and may play a role in the regulation of bone metabolism. Here we demonstrate that pharmacological blockade of ligand signaling through the high affinity receptor for activin, type II activin receptor (ActRIIA), by administration of the soluble extracellular domain of ActRIIA fused to a murine IgG2a-Fc, increases bone formation, bone mass, and bone strength in normal mice and in ovariectomized mice with established bone loss. These observations support the development of this pharmacological strategy for the treatment of diseases with skeletal fragility.

Biology of breast cancer bone metastasis.

Abstract: Breast carcinoma ranks among the most prevalent malignancies in women. Breast carcinoma frequently metastasizes to bone and approximately 70% of patients with breast cancer have bone metastases, which generally are osteolytic lesions. They cause major morbidity and mortality in patients; and the available treatment options are limited. Bone-specific homing and colonization of cancer cells are important and interesting features of metastasis. There are complex and multiple steps in the process of bone metastasis; and the elaborate interaction between breast carcinoma and bone involves various cytokines, growth factors and cellular signals, which results in a vicious cycle and promotes tumor cell accumulation and osteolysis. Recent advances in molecular biology have resulted in major breakthroughs in our understanding of the pathogenesis of bone metastasis in breast cancer, which is critical in preventing metastasis, designing novel and targeted treatments and prolonging survival in this devastating condition.

Relative importance of errors in left ventricular quantitation by two-dimensional echocardiography: insights from three-dimensional echocardiography and cardiac magnetic resonance imaging.

Abstract: Background The accuracy of left ventricular (LV) volumes and ejection fraction (EF) on two-dimensional echocardiography (2DE) is limited by image position (IP), geometric assumption (GA), and boundary tracing (BT) errors. Methods Real-time three-dimensional echocardiography (RT3DE) and cardiac magnetic resonance imaging (CMR) were used to determine the relative contribution of each error source in normal controls (n = 35) and patients with myocardial infarctions (MIs) (n = 34). LV volumes and EFs were calculated using (1) apical biplane disk summation on 2DE (IP + GA + BT errors), (2) biplane disk summation on RT3DE (GA + BT errors), (3) 4-multiplane to 8-multiplane surface approximation on RT3DE (GA + BT errors), (4) voxel-based surface approximation on RT3DE (BT error alone) and (5) CMR. By comparing each method with CMR, the absolute and relative contributions of each error source were determined. Results IP error predominated in LV volume quantification on 2DE in normal controls, whereas GA error predominated in patients with MIs. Underestimation of volumes on 2DE was overcome by increasing the number of imaging planes on RT3DE. Although 4 equidistant image planes were acceptable, the best results were achieved with voxel-based RT3DE. For EF estimation, IP error predominated in normal controls, whereas BT error predominated in patients with MIs. Nevertheless, one third of the EF estimation error in patients with MIs was due to a combination of IP and GA errors, both of which may be addressed using RT3DE. Conclusions The relative contribution of each source of LV quantitation error on 2DE was defined and quantified. Each source of error differed depending on patient characteristics and LV geometry.

Coronary calcium coverage score: determination, correlates, and predictive accuracy in the Multi-Ethnic Study of Atherosclerosis.

Abstract: Purpose: To develop a new calcium score for use with unenhanced cardiac computed tomography (CT) that can be used to define the percentage of coronary arteries affected by calcium and to correlate this score with risk factors and cardiovascular events. Materials and Methods: Institutional review boards at all participating centers approved this HIPAA-compliant study, and all participants gave written informed consent. Calcium coverage score (CCS), which represents the percentage of coronary arteries affected by calcific plaque, was calculated for 3252 participants in the Multi-Ethnic Study of Atherosclerosis in whom calcific plaque was detected with CT. Quasi-Poisson models were used to estimate associations (assessed by using t tests with robust standard errors) between CCS and risk factors. Associations between the CCS, Agatston, and calcium mass scores (hereafter, mass scores) and outcomes were estimated and assessed by using Cox proportional hazards models with Wald tests. The predictive ability of th...

Accuracy of dose measurements and calculations within and beyond heterogeneous tissues for 6 MV photon fields smaller than 4 cm produced by Cyberknife

Abstract: For the small radiation field sizes used in stereotactic radiosurgery, lateral electronic disequilibrium and steep dose gradients exist in a large portion of these fields, requiring the use of high-resolution measurement techniques. These relatively large areas of electronic disequilibrium make accurate dosimetry as well as dose calculation more difficult, and this is exacerbated in regions of tissue heterogeneity. Tissue heterogeneity was considered insignificant in the brain where stereotactic radiosurgery was first used. However, as this technique is expanded to the head and neck and other body sites, dose calculations need to account for dose perturbations in and beyond air cavities, lung, and bone. In a previous study we have evaluated EBT Gafchromic film (International Specialty Products, Wayne, NJ) for dosimetry and characterization of the Cyberknife radiation beams and found that it was comparable to other common detectors used for small photon beams in solid water equivalent phantoms. In the present work EBT film is used to measure dose in heterogeneous slab phantoms containing lung and bone equivalent materials for the 6 MV radiation beams of diameter 7.5 to 40 mm produced by the Cyberknife (Accuray, Sunnyvale, CA). These measurements are compared to calculations done with both the clinically utilized Raytrace algorithm as well as the newly developed Monte Carlo based algorithm available on the Cyberknife treatment planning system. Within the low density material both the measurements and Monte Carlo calculations correctly model the decrease in dose produced by a loss of electronic equilibrium, whereas the Raytrace algorithm incorrectly predicts an enhancement of dose in this region. Beyond the low density material an enhancement of dose is correctly calculated by both algorithms. Within the high density bone heterogeneity the EBT film measurements represent dose to unit density tissue in bone and agree with the Monte Carlo results when corrected to dose to unit density tissue in bone. We conclude that EBT film is an appropriate dosimeter for measuring dose in heterogeneous materials and these measurements agree with Monte Carlo calculations of dose as implemented in the Cyberknife treatment planning system.

An exploration of the determinants of reporting crime to the police in the city of tianjin, china*

Abstract: Western research has investigated three types of correlates of crime reporting–victim-specific (individual or household), incident-specific, and environment-specific variables. The current study applies this general, analytical framework to explore the determinants of crime reporting to the police in contemporary urban China. Using data collected from a recent survey of criminal victimization in Tianjin, we assess the determinants for reporting of robbery, assault, personal theft, and household burglary. The results consistently show that offense seriousness is a significant predictor of reporting for all offenses studied. Also, a nonlinear relationship between neighborhood disadvantage and reporting of burglary is found. In contrast, individual-specific and household-specific factors do not affect reporting, with the exception of a cumulative measure of victimization experience. Measures of neighborhood social cohesion and informal control are also not associated with reporting. The implications of these findings are discussed with reference to the unique neighborhood organizational infrastructure in urban China.

PPARG by Dietary Fat Interaction Influences Bone Mass in Mice and Humans

Abstract: Adult BMD, an important risk factor for fracture, is the result of genetic and environmental interactions. A quantitative trait locus (QTL) for the phenotype of volumetric BMD (vBMD), named Bmd8, was found on mid-distal chromosome (Chr) 6 in mice. This region is homologous to human Chr 3p25. The B6.C3H-6T (6T) congenic mouse was previously created to study this QTL. Using block haplotyping of the 6T congenic region, expression analysis in the mouse, and examination of nonsynonymous SNPs, peroxisome proliferator activated receptor γ (Pparg) was determined to be the most likely candidate gene for the Bmd8 QTL of the 630 genes located in the congenic region. Furthermore, in the C3H/HeJ (C3H) strain, which is the donor strain for the 6T congenic, several polymorphisms were found in the Pparg gene. On challenge with a high-fat diet, we found that the 6T mouse has a lower areal BMD (aBMD) and volume fraction of trabecular bone (BV/TV%) of the distal femur compared with B6 mice. Interactions between SNPs in the PPARG gene and dietary fat for the phenotype of BMD were examined in the Framingham Offspring Cohort. This analysis showed that there was a similar interaction of the PPARG gene and diet (fat intake) on aBMD in both men and women. These findings suggest that dietary fat has a significant influence on BMD that is dependent on the alleles present for the PPARG gene.

Laparoscopic revision of Nissen fundoplication to Roux-en-Y gastric bypass in morbidly obese patients.

Abstract: Background We present a case of a morbidly obese patient with previous laparoscopic Nissen fundoplication (LNF) who was successfully treated by revision to a laparoscopic Roux-en-Y gastric bypass (RYGB) and discuss our collective experience.

Pulmonary Manifestations of Primary Sjögren's Syndrome

Abstract: Sjogren's syndrome (SS) is a systemic disease with a predilection for the exocrine glands. It also is considered to be an autoimmune epitheliitis, and, as the respiratory system is lined throughout with epithelial cells, it should not be surprising that patients who have SS may develop pulmonary disease. This article describes these manifestations.

Skeletal overexpression of connective tissue growth factor impairs bone formation and causes osteopenia.

Abstract: Connective tissue growth factor (CTGF), a member of the CCN family of proteins, is expressed in skeletal cells, and the ctgf null mutation leads to neonatal lethality due to defects in skeletal development. To define the function of CTGF in the postnatal skeleton, we created transgenic mice overexpressing CTGF under the control of the human osteocalcin promoter. CTGF transgenic female and male mice exhibited a significant decrease in bone mineral density, compared with wild-type littermate controls. Bone histomorphometry revealed that CTGF overexpression caused decreased trabecular bone volume due to impaired osteoblastic activity because mineral apposition and bone formation rates were decreased. Osteoblast and osteoclast number and bone resorption were not altered. Calvarial osteoblasts and stromal cells from CTGF transgenics displayed decreased alkaline phosphatase and osteocalcin mRNA levels and reduced bone morphogenetic protein (BMP) signaling mothers against decapentaplegic, Wnt/β-catenin, and IGF-I/Akt signaling. In conclusion, CTGF overexpression in vivo causes osteopenia, secondary to decreased bone formation, possibly by antagonizing BMP, Wnt, and IGF-I signaling and activity.

Juvenile delinquency and justice in contemporary China: a critical review of the literature over 15 years

Abstract: The study reviews research on juvenile delinquency and justice in China since 1990. The review covers three issues that have been studied in the publications: (1) the nature and scope of China’s juvenile delinquency; (2) individual, group, and institutional factors and their roles in delinquency involvement; and (3) the development of China’s juvenile justice. Because Hong Kong is a special region of China and has a different social, political, and legal system, the study reviews the publications on Hong Kong’s juvenile delinquency and justice in a separate section. It summarizes the findings derived from the review, analyzes and discusses the limitations of the reviewed studies, and provides prospects for future research in the area.

A critical review of recent literature on crime and criminal justice in China: research findings, challenges, and prospects (Introduction)

Abstract: BackgroundCriminological research was virtually non-existent in China from the time that theCommunists took power in 1949 up until the nation initiated the economic reformand “open door” policy in the 1980s. This neglect was due in part to the Communistideology that crimes, especially street-level crimes, are not compatible with asocialist society. In addition, levels of these types of crime were by all accounts verylow. Political directives warned the Chinese people to stay clear of any criminalinvolvement. As a result, China enjoyed very low crime rates and was characterizedby some as a virtually “crime-free” society [2, 5]. Criminological enterprise was notvery prevalent.However, since China implemented its economic reform and open door policy,the level of criminal behavior has been increasing. Official statistics reported a 340%increase of total crime and a tenfold increase in serious crime from 1979 to 1990 [1,5]. In 1978, the crime rate was 55.91 per 100,000; it reached 355.5 per 100,000 in2005 [4]. The increases in crime combined with the ascendance of China as aneconomic superpower have attracted many scholars to the field of crime and criminaljustice. China provides a great opportunity for Chinese and Western researchers toadvance knowledge and understanding of crime and criminal justice in a differentsocial and cultural setting where there had been virtually no criminological researchfor a long time. Consequently, studies on China’s crime and criminal justice have

The mutation ROR2W749X, linked to human BDB, is a recessive mutation in the mouse, causing brachydactyly, mediating patterning of joints and modeling recessive Robinow syndrome.

Abstract: Mutations in ROR2 result in a spectrum of genetic disorders in humans that are classified, depending on the nature of the mutation and the clinical phenotype, as either autosomal dominant brachydactyly type B (BDB, MIM 113000) or recessive Robinow syndrome (RRS, MIM 268310). In an attempt to model BDB in mice, the mutation W749X was engineered into the mouse Ror2 gene. In contrast to the human situation, mice heterozygous for Ror2(W749FLAG) are normal and do not develop brachydactyly, whereas homozygous mice exhibit features resembling RRS. Furthermore, both Ror2(W749FLAG/W749FLAG) and a previously engineered mutant, Ror2(TMlacZ/TMlacZ), lack the P2/P3 joint. Absence of Gdf5 expression at the corresponding interzone suggests that the defect is in specification of the joint. As this phenotype is absent in mice lacking the entire Ror2 gene, it appears that specification of the P2/P3 joint is affected by ROR2 activity. Finally, Ror2(W749FLAG/W749FLAG) mice survive to adulthood and exhibit phenotypes (altered body composition, reduced male fertility) not observed in Ror2 knockout mice, presumably due to the perinatal lethality of the latter. Therefore, Ror2(W749FLAG/W749FLAG) mice represent a postnatal model for RRS, provide insight into the mechanism of joint specification, and uncover novel roles of Ror2 in the mouse.

Self-reported comorbidities among self-described overweight African-American and Hispanic adults in the United States: results of a national survey.

Abstract: Objective: To examine the concordance between self-described weight status and BMI, the prevalence of self-reported comorbidities, and the association between comorbidities and self-rated health among overweight African-American and Hispanic US adults. Methods and Procedures: A nationally representative sample of 537 African-American and 526 Hispanic adults who were identified using a combination of random digit dialing and listed household sampling and self-described as being slightly or very overweight participated in a telephone interview. Self-reported height and weight were used to calculate BMI. Results: More than half of African Americans (56%) and one-third of Hispanics (34%) who self-described as “slightly” overweight would be classified as obese based on BMI. One-third (33%) of African Americans reported high blood pressure, followed by arthritis (20%), high cholesterol (18%), and diabetes (15%). Among Hispanics, high cholesterol was the most frequently reported comorbidity (17%), followed by high blood pressure (15%), and difficulty sleeping (12%). Almost three-quarters of African Americans surveyed (72%) reported that their overall health was good to excellent compared to 62% for Hispanics. Discussion: Self-reported rates of obesity-related comorbidities fall below what would be expected based on prevalence data derived from physiologic measures, suggesting a lack of awareness of actual risk. Despite the greater self-reported prevalence of certain risk factors for poor health, African Americans have a more optimistic view of their overall health and weight status compared to Hispanics. Physicians have an important opportunity to communicate to their minority patients the serious health consequences associated with excess weight.

Fat-water separated delayed hyperenhanced myocardial infarct imaging.

Abstract: Fat deposition associated with myocardial infarction (MI) has been reported as a commonly occurring phenomenon. Magnetic resonance imaging (MRI) has the ability to efficiently detect MI using T1-sensitive contrast-enhanced sequences and fat via its resonant frequency shift. In this work, the feasibility of fat-water separation applied to the conventional delayed hyperenhanced (DHE) MI imaging technique is demonstrated. A three-point Dixon acquisition and reconstruction was combined with an inversion recovery gradient-echo pulse sequence. This allowed fat-water separation along with T1 sensitive imaging after injection of a gadolinium contrast agent. The technique is demonstrated in phantom experiments and three subjects with chronic MI. Areas of infarction were well defined as conventional hyperenhancement in water images. In two cases, fatty deposition was detected in fat images and confirmed by precontrast opposed-phase imaging. Magn Reson Med 60:503–509, 2008. © 2008 Wiley-Liss, Inc.

Pressure Ulcer Development in Infants: State of the Science

Abstract: The science of pressure ulcer development in infants is underdeveloped. Although recent conceptual frameworks have been applied to younger populations, this article focuses on the unique attributes of full-term and preterm newborns that have an impact on pressure ulcer development. A proposed schema identifies the theoretical elements associated with pressure ulcer development in infants.

Activation of the ERK pathway in osteoblastic cells, role of gremlin and BMP-2.

Abstract: Gremlin is a glycoprotein that binds and antagonizes the actions of bone morphogenetic proteins (BMPs) -2, -4, and -7. Gremlin appears to activate the extracellular regulated kinase (ERK) pathway in endothelial and tumor cells, and as a consequence to have direct cellular effects. To determine whether gremlin has direct effects in osteoblasts, independent of its BMP binding activity, we examined its effects in ST-2 murine stromal cell lines and in primary cultures of murine calvarial osteoblasts. Gremlin did not activate Signaling mothers against decapentaplegic (Smad), and suppressed the BMP-2 induced Smad 1/5/8 phosphorylation and the transactivation of the BMP/Smad reporter construct 12xSBE-Oc-pGL3, confirming its BMPs antagonizing activity. Neither gremlin nor BMP-2 induced ERK 1/2 activation in ST-2 cells or calvarial osteoblasts. Moreover, slight changes in culture conditions induced the phosphorylation of ERK independent from BMP or gremlin exposure. In conclusion, gremlin inhibits BMP-2 signaling and activity, and does not have independent actions on ERK signaling in osteoblasts. Consequently, gremlin activity in osteoblasts can be attributed only to its BMP antagonizing effects.

A retrospective randomized study of asthma control in the US: results of the CHARIOT study

Abstract: Background: The third version of the National Asthma Education and Prevention Program (NAEPP) Expert Panel Report (EPR-3): Guidelines on the Diagnosis and Management of Asthma emphasizes the need to use asthma control rather than patient severity to base adjustments to treatment and ultimately improve patient outcomes. The objectives of the current study were to assess control of patients with moderate-to-severe asthma, examine the natural history of the disease, practice patterns and resource utilization in specialty community practices according to recently reviewed NAEPP guidelines. Research design and methods: This analysis represents a retrospective, multicenter, randomized study of 1009 patient charts in sixty United States allergy and pulmonary medicine community practices. The proportion of patients with controlled and uncontrolled asthma over 12 months, prevalence and characteristics of atopy, past asthma history, pulmonary function, medications and treatment patterns, patient and clinical practice characteristics were analyzed. Main outcome measures: The primary outcome of interest was asthma control.

Globalizing Beauty: Attitudes toward Beauty Pageants among Nepali Women

Abstract: A series of focus groups and semi-structured interviews were conducted exploring the beliefs of urban Nepali women about the introduction of beauty pageants to Nepal. This qualitative study examine...

Comparing Recreation Benefits from On-Site versus Household Surveys in Count Data Travel Cost Demand Models with Overdispersion:

Abstract: On-site surveys of tourists often lead to overestimates of annual tourism because tourists who are frequent repeat visitors are more likely to be sampled. This unrepresentative sample leads to statistical problems known as ‘truncation’ and ‘endogenous stratification’ in widely used travel cost demand models. Further, wide variation in the number of on-site visits among tourists can lead to overdispersion in the dependent variable of count data travel cost models. The authors present the first real-world data correction for all three problems and compare the corrected estimates with the ideal household survey. Correcting for truncation and endogenous stratification in a count data specification allowing for overdispersion (negative binomial specification) lowers the demand and benefit estimate to a mean value not significantly different from the household estimate. If tourism researchers wish to develop visitor use estimates from on-site surveys consistent with household level surveys, the authors' improve...

Criminal victimization in contemporary China: a review of the evidence and challenges for future research

Abstract: The rapid economic growth in China over recent decades has been accompanied by higher levels of crime, but there have been few studies of the Chinese experience of criminal victimization. A recent victimization survey of a representative sample of households in Tianjin represents a major effort to fill this gap in the literature. The present paper reviews the research based on the Tianjin survey along with other studies of crime and criminal victimization in China that have been published since 1990. We summarize the major findings, discuss the theoretical perspectives and methodological strategies that have been applied, identify the limitations of the research to date, and offer suggestions for future research.

An FBN1 pseudoexon mutation in a patient with Marfan syndrome: Confirmation of cryptic mutations leading to disease

Abstract: Marfan syndrome (MFS) results from heterozygous mutations in FBN1. However, genetic analyses of deoxyribonucleic acid (DNA) from approximately 10–30% of MFS patients who meet diagnostic criteria do not reveal an identifiable FBN1 mutation. In a patient who met the diagnostic criteria for MFS, bidirectional DNA sequencing of exons and intron–exon boundaries of FBN1 failed to reveal a mutation. Assessment of the FBN1 message in dermal fibroblasts from the patient revealed insertion of a pseudoexon between exons 63 and 64. Sequencing of intron 63 identified a point mutation, IVS63+373, located near the middle of intron 63 of FBN1 that created a donor splice site in intron 63, leading to inclusion of a 93-bp fragment of intronic sequence in the FBN1 message. Identification of a novel pseudoexon mutation in FBN1, in association with a clinical diagnosis of MFS, confirms that cryptic mutations that are missed by the current DNA-based diagnostic methods have a causative role.