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S A Rasmussen

Publications and source records attributed to S A Rasmussen.

At least 19 recordsLinked to original sources
PubMed2006

Genomewide linkage scan for obsessive-compulsive disorder: evidence for susceptibility loci on chromosomes 3q, 7p, 1q, 15q, and 6q.

Obsessive-compulsive disorder (OCD) is the tenth most disabling medical condition worldwide. Twin and family studies implicate a genetic etiology for this disorder, although specific genes have yet to be identified. Here, we present the first large-scale model-free linkage analysis of both extended and nuclear families using both 'broad' (definite and probable diagnoses) and 'narrow' (definite only) definitions of OCD. We conducted a genome-scan analysis of 219 families collected as part of the OCD Collaborative Genetics Study. Suggestive linkage signals were revealed by multipoint analysis on chromosomes 3q27-28 (P=0.0003), 6q (P=0.003), 7p (P=0.001), 1q (P=0.003), and 15q (P=0.006). Using the 'broad' OCD definition, we observed the strongest evidence for linkage on chromosome 3q27-28. The maximum overall Kong and Cox LODall score (2.67) occurred at D3S1262 and D3S2398, and simulation based P-values for these two signals were 0.0003 and 0.0004, respectively, although for both signals, the simulation-based genome-wide significance levels were 0.055. Covariate-linkage analyses implicated a possible role of gene(s) on chromosome 1 in increasing the risk for an earlier onset form of OCD. We are currently pursuing fine mapping in the five regions giving suggestive signals, with a particular focus on 3q27-28. Given probable etiologic heterogeneity in OCD, mapping gene(s) involved in the disorder may be enhanced by replication studies, large-scale family-based linkage studies, and the application of novel statistical methods.

Chromosomes, Human↗
PubMed2002

Gliomas presenting after age 10 in individuals with neurofibromatosis type 1 (NF1).

Children with neurofibromatosis 1 (NF1) often develop low-grade gliomas, but brain tumors are infrequently encountered in adults with NF1. The authors present evidence from two clinical series, one including patients known to have NF1 and another focusing on adults with new onset brain tumors, that suggests an association between NF1 and symptomatic gliomas in older individuals. They also summarize the clinical data on 17 adolescents or adults with NF1 and symptomatic gliomas. The findings suggest that individuals with NF1 are at increased risk of developing gliomas throughout their lives.

Adolescent↗
PubMed2001

The use of antibody D8/17 to identify B cells in adults with obsessive-compulsive disorder.

Compared with healthy control subjects, individuals with childhood-onset obsessive-compulsive disorder (OCD) have been reported to have a higher percentage of B cells that react with the monoclonal antibody D8/17, a marker for rheumatic fever. This study sought to replicate these findings in adults with OCD. Double-blind analyses of blood samples from 29 consecutive adults with primary OCD and 26 healthy control subjects were conducted to determine the percentage of B cells identified by D8/17. Using a standard criterion of > or =12% labeled B cells to denote positivity, rates of D8/17 positive individuals did not significantly differ between the OCD (58.6%) and control (42.3%) groups. Early age of onset was not a predictor of D8/17 positivity in the OCD group. The percentage of B cells identified by the monoclonal antibody marker D8/17 did not distinguish adults with OCD from control subjects, nor did it distinguish a sub-group of adults with OCD who described pre-pubertal onset of their OCD symptoms.

Adolescent↗
PubMed2001

Mortality in neurofibromatosis 1: an analysis using U.S. death certificates.

Although neurofibromatosis 1 (NF1) is a relatively common autosomal dominant condition, information about its effect on mortality is limited. We used Multiple-Cause Mortality Files, compiled from U.S. death certificates by the National Center for Health Statistics, for 1983 through 1997. We identified 3,770 cases of presumed NF1 among 32,722,122 deaths in the United States, a frequency of 1/8,700, which is one-third to one-half the estimated prevalence. Mean and median ages at death for persons with NF1 were 54.4 and 59 years, respectively, compared with 70.1 and 74 years in the general population. Results of proportionate mortality ratio (PMR) analyses showed that persons with NF1 were 34 times more likely (PMR=34.3, 95% confidence interval [CI] 30.8-38.0) to have a malignant connective or other soft-tissue neoplasm listed on their death certificates than were persons without NF1. Overall, persons with NF1 were 1.2 times more likely than expected (PMR=1.21, 95% CI 1.14-1.28) to have a malignant neoplasm listed on their death certificates, but the PMR was 6.07 (95% CI 4.88-7.45) for persons who died at 10-19 years of age and was 4.93 (95% CI 4.14-5.82) for those who died at 20-29 years of age. Similarly, vascular disease was recorded more often than expected on death certificates of persons with NF1 who died at <30 years of age (PMR=3.26, 95% CI 1.31-6.71 at age <10 years; PMR=2.68, 95% CI 1.38-4.68 at age 10-19 years; and PMR=2.25, 95% CI 1.46-3.32 at 20-29 years) but not in older persons. This study supports previous findings of decreased life expectancy for persons with NF1 and, within the limitations of death certificates, provides population-based data about NF1 morbidity and mortality that are useful to clinicians caring for patients with NF1.

Adolescent↗
PubMed2001

Effective coding in birth defects surveillance.

Effective coding is critical to data collected by birth defects surveillance programs because subsequent use of the data depends on storage and retrieval of cases using codes. Hence, careful consideration needs to be given to the coding process. The primary goal of coding is to accurately, completely, and concisely represent infants with birth defects. Coding procedures need to accommodate the objectives of the surveillance program; for example, programs that focus on research may require different coding procedures from those that focus on linking infants to services. Several challenges exist in coding birth defects, including the need to distinguish infants with multiple defects and syndromes from those with isolated defects, and the need for strategies to code suspected defects for which confirmation is not available. Selection of a coding system by a birth defects surveillance program is central to the utility of the data collected. Most programs use a modification of the International Statistical Classification of Diseases and Related Health Problems-based (ICD) systems. This paper addresses ICD-based systems and the modifications used by many birth defects surveillance programs and presents examples of the problems in interpreting birth defects data because of inappropriate coding.

Congenital Abnormalities↗
PubMed2001

Risk for birth defects among premature infants: a population-based study.

OBJECTIVE: To investigate the relationship between prematurity and birth defects. STUDY DESIGN: In a population-based cohort study, infants with birth defects were ascertained through the Metropolitan Atlanta Congenital Defects Program, a surveillance system with active methods of ascertainment. Gestational age data were obtained from birth certificates of liveborn, singleton infants with and without birth defects born in the 5-county metropolitan Atlanta area. RESULTS: Among 264,392 infants with known gestational ages born between 1989 and 1995, 7738 were identified as having birth defects (2.93%). Premature infants (<37 weeks' gestation) were more than two times as likely to have birth defects than term infants (37-41 weeks) (risk ratio = 2.43; 95% CI 2.30-2.56). This relationship was evident for several categories of birth defects. The rate of birth defects varied by gestational age categories, with the highest risk in the 29- to 32-week gestational age category (risk ratio = 3.37). CONCLUSIONS: The risk for birth defects is increased in premature infants. Awareness of this relationship is important for clinicians caring for premature infants. The morbidity and mortality associated with a particular defect may be significantly altered by the presence of prematurity. Further study of this association may provide insight into the etiology of these relatively common problems.

Cohort Studies↗
PubMed2001

The National Birth Defects Prevention Study.

The National Birth Defects Prevention Study was designed to identify infants with major birth defects and evaluate genetic and environmental factors associated with the occurrence of birth defects. The ongoing case-control study covers an annual birth population of 482,000 and includes cases identified from birth defect surveillance registries in eight states. Infants used as controls are randomly selected from birth certificates or birth hospital records. Mothers of case and control infants are interviewed and parents are asked to collect buccal cells from themselves and their infants for DNA testing. Information gathered from the interviews and the DNA specimens will be used to study independent genetic and environmental factors and gene-environment interactions for a broad range of birth defects. As of December 2000, 7,470 cases and 3,821 controls had been ascertained in the eight states. Interviews had been completed with 70% of the eligible case and control mothers, buccal cell collection had begun in all of the study sites, and researchers were developing analysis plans for the compiled data. This study is the largest and broadest collaborative effort ever conducted among the nation's leading birth defect researchers. The unprecedented statistical power that will result from this study will enable scientists to study the epidemiology of some rare birth defects for the first time. The compiled interview data and banked DNA of approximately 35 categories of birth defects will facilitate future research as new hypotheses and improved technologies emerge.

Case-Control Studies↗
PubMed2001

Delusionality and response to open-label fluvoxamine in body dysmorphic disorder.

BACKGROUND: Available data suggest that the delusional variant of body dysmorphic disorder (BDD), a type of delusional disorder, may respond to serotonin reuptake inhibitors (SRIs) and that delusionality (lack of insight) in BDD may improve with SRI treatment. However, this research has been hampered by the lack of a reliable and valid scale to assess delusionality. METHOD: Thirty subjects (21 women, 9 men; mean age = 33.3 +/- 9.0 years) with DSM-IV BDD were prospectively treated with open-label fluvoxamine for 16 weeks. Subjects were assessed at regular intervals with the Brown Assessment of Beliefs Scale (BABS), the Yale-Brown Obsessive Compulsive Scale Modified for BDD (BDD-YBOCS; a measure of BDD severity), and other instruments. The BABS is a reliable and valid 7-item, semistructured, clinician-administered scale that assesses current delusionality. RESULTS: In this prospective, open-label study, 63% of BDD subjects responded to fluvoxamine. Delusional and nondelusional subjects had similar improvement in BDD symptoms. In addition, insight significantly improved in both delusional and nondelusional subjects. Baseline BABS scores did not contribute significantly to endpoint BDD-YBOCS scores in a regression analysis. CONCLUSION: Degree of delusionality did not predict fluvoxamine response, and delusionality significantly improved. These findings are preliminary and require confirmation in controlled trials. The implications of these findings for other types of delusions requires investigation.

Adult↗
PubMed2000

NF1 gene and neurofibromatosis 1.

Neurofibromatosis 1 (NF1), also known as von Recklinghausen disease, is an autosomal dominant condition caused by mutations of the NF1 gene, which is located at chromosome 17q11.2. NF1 is believed to be completely penetrant, but substantial variability in expression of features occurs. Diagnosis of NF1 is based on established clinical criteria. The presentation of many of the clinical features is age dependent. The average life expectancy of patients with NF1 is probably reduced by 10-15 years, and malignancy is the most common cause of death. The prevalence of clinically diagnosed NF1 ranges from 1/2,000 to 1/5,000 in most population-based studies. A wide variety of NF1 mutations has been found in patients with NF1, but no frequently recurring mutation has been identified. Most studies have not found an obvious relation between particular NF1 mutations and the resulting clinical manifestations. The variability of the NF1 phenotype, even in individuals with the same NF1 gene mutation, suggests that other factors are involved in determining the clinical manifestations, but the nature of these factors has not yet been determined. Laboratory testing for NF1 mutations is difficult. A protein truncation test is commercially available, but its sensitivity, specificity, and predictive value have not been established. No general, population-based molecular studies of NF1 mutations have been performed. At this time, it appears that the benefits of population-based screening for clinical features of NF1 would not outweigh the costs of screening.

Chromosomes, Human, Pair 17↗
PubMed2000

Clinical features of obsessive-compulsive disorder.

The past decade has seen tremendous strides in the knowledge about the cause, epidemiology, and treatment of OCD. Research on clinical characteristics of the disorder have focused on several areas, including identification of subtypes, the role of insight, and patterns of comorbidity. Several studies looking at course of illness in OCD have found that, for adults with this disorder, the course is usually chronic, but increasing evidence shows that a subtype of OCD characterized by an episodic course may exist, and research is focusing on delineating that subtype more specifically. Another hypothesized subtype, which may be related to rheumatic fever, involves patients with both OCD and chronic tic disorders. Certain obsessions and compulsions are more common in patients with these two disorders; together with the familial transmission and treatment data, this suggests that these patients may represent a meaningful subtype. Another area of focus over the past 10 years has been the role of insight. Increasing evidence shows that a range of insight exists in patients with OCD. Whether patients with poor insight have a different treatment response or different course than do patients with better insight remains to be seen. Finally, comorbidity between OCD and schizophrenia has been an area of interest. Emerging evidence shows that obsessions and compulsions are more common in patients with schizophrenia than was previously thought. The effect of obsessions and compulsions on schizophrenia in terms of treatment response and course is being investigated. Despite tremendous advances in treatment of this potentially debilitating disorder, a significant percentage of patients do not respond to standard treatment. Continued research to identify meaningful subtypes in OCD is necessary to unravel important questions concerning cause and to develop specific treatment strategies for refractory patients.

Adult↗
PubMed2000

Neuroanatomically based approaches to obsessive-compulsive disorder. Neurosurgery and transcranial magnetic stimulation.

Obsessive-compulsive disorder is a severe condition. Unfortunately, current medication and behavior therapies fail to adequately benefit some patients most severely affected. Advancing knowledge of brain circuit involvement has potential treatment implications. The neurosurgical techniques most often used in the United States for crippling, treatment-refractory obsessive-compulsive disorder are reviewed in the context of anatomic models of the illness. The use of transcranial magnetic stimulation to probe possible neuroanatomic and neurophysiologic substrates of this disorder is considered, and how the knowledge gained from such studies might advance treatment is presented.

Brain↗
PubMed2000

Culture of cytogenetically abnormal schwann cells from benign and malignant NF1 tumors.

Dermal and plexiform neurofibromas are benign peripheral nerve sheath tumors that arise in neurofibromatosis type 1 (NF1). NF1 patients also have an increased risk of malignant peripheral nerve sheath tumors (MPNSTs), thought to arise in a subset of plexiform neurofibromas. Plexiform neurofibroma pathogenesis is poorly understood, despite the serious clinical problem posed by these tumors. The Schwann cell is hypothesized to be the cell type initially mutated and clonally expanded in plexiform neurofibromas. To test this hypothesis and search for genetic alterations involved in tumorigenesis, we established Schwann cell cultures from plexiform and dermal neurofibromas. Cytogenetic abnormalities were identified in 4/6 plexiform cultures (including one from a plexiform with a sarcomatous component) and 0/7 dermal neurofibroma Schwann cell cultures. There were no consistent chromosomal regions involved in the abnormal karyotypes, suggesting that plexiform tumors are heterogeneous and may bear a variety of primary and/or secondary genetic changes. This is the first study to show successful culturing of genetically abnormal Schwann cell lineages from plexiform neurofibromas. Thus, we present the strongest evidence yet to support the theory that the Schwann cell is the central component in the development of plexiform neurofibromas. This is a key finding for NF1 research, which will lead to further studies of the genetic and biochemical pathogenesis of these Schwann cell tumors. Genes Chromosomes Cancer 27:117-123, 2000.

Cell Division↗
PubMed2000

Chromosome 17 loss-of-heterozygosity studies in benign and malignant tumors in neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1) is a common autosomal dominant condition characterized by benign tumor (neurofibroma) growth and increased risk of malignancy. Dermal neurofibromas, arising from superficial nerves, are primarily of cosmetic significance, whereas plexiform neurofibromas, typically larger and associated with deeply placed nerves, extend into contiguous tissues and may cause serious functional impairment. Malignant peripheral nerve sheath tumors (MPNSTs) seem to arise from plexiform neurofibromas. The NF1 gene, on chromosome segment 17q11.2, encodes a protein that has tumor suppressor function. Loss of heterozygosity (LOH) for NF1 has been reported in some neurofibromas and NF1 malignancies, but plexiform tumors have been poorly represented. Also, the studies did not always employ the same markers, preventing simple comparison of the frequency and extent of LOH among different tumor types. Our chromosome 17 LOH analysis in a cohort of three tumor types was positive for NF1 allele loss in 2/15 (13%) dermal neurofibromas, 4/10 (40%) plexiform neurofibromas, and 3/5 (60%) MPNSTs. Although the region of loss varied, the p arm (including TP53) was lost only in malignant tumors. The losses in the plexiform tumors all included sequences distal to NF1. No subtle TP53 mutations were found in any tumors. This study also reports the identification of both NF1 "hits" in plexiform tumors, further supporting the tumor suppressor role of the NF1 gene in this tumor type.

Adolescent↗
PubMed1999

Segregation analysis of obsessive-compulsive disorder using symptom-based factor scores.

Obsessive-compulsive disorder (OCD) is a complex psychiatric disorder characterized by recurring obsessions or compulsions that cause significant distress to the patient or significantly interfere with the patient's normal home, work, or social activities [Diagnostic and Statistical Manual of Mental Disorders, 4th Edition. Washington, DC: American Psychiatric Association, 1994]. Twin and family studies have suggested that OCD has a significant genetic component. We performed complex segregation analyses using POINTER with families ascertained through an OCD-affected proband. In an attempt to resolve the phenotypic heterogeneity observed among individuals with OCD these segregation analyses used four factor-analytic symptom dimensions to subset the family sample based upon probands' symptom factor scores. Analysis of the entire sample allowed rejection of only the no transmission model; that model was also rejected in all subsequent analyses. Limiting the analyses to families with at least one OCD-affected member in addition to the proband (the demonstrably familial form of OCD) allowed rejection of all models except the mixed model. Analyses limited to families of high-factor-3 (symmetry and ordering symptoms) probands led to rejection of the polygenic model, indicating the involvement of a major locus. Additionally, the relative risk of OCD or subclinical OCD was 1.7 for relatives of probands with a factor 3 score greater than zero compared with relatives of probands with a low factor score. The symptoms attributed to high factor 3 scores (symmetry and ordering) may constitute a genetically significant symptomatic subtype of OCD. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:669-675, 1999.

Aging↗