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Bruce R Korf

Publications and source records attributed to Bruce R Korf.

At least 19 recordsLinked to original sources
PubMed2025

Genotype-first assessment of presentation and penetrance of neurofibromatosis type 1, autosomal dominant polycystic kidney disease, and Marfan syndrome within the All of Us research program cohort.

PURPOSE: Phenotype-based ascertainment of probands in studies of Mendelian disorders may exclude individuals with mild phenotypes or that lack health care access. We explore this premise in All of Us Research Program participants with pathogenic variation causal for 3 Mendelian conditions: autosomal dominant polycystic kidney disease (ADPKD), Marfan syndrome, and neurofibromatosis type 1 (NF1). METHODS: We identified All of Us Research Program participants with putatively pathogenic variation in NF1, FBN1, PKD1, and PKD2. Concept terms were extracted from electronic health records to assess participant diagnosis and phenotype. Variant annotation and participant surveys were evaluated to identify biological and social factors differentiating diagnosed and undiagnosed individuals. RESULTS: Large proportions of individuals with pathogenic variation in NF1, FBN1, or PKD1/PKD2 lack the associated diagnosis of NF1 (47%), Marfan syndrome (58%), or ADPKD (52%), respectively. Pathogenic variants in diagnosed individuals have greater inferred deleteriousness for NF1 and ADPKD, and undiagnosed individuals had less severe phenotypes compared with diagnosed individuals for all 3 conditions. CONCLUSION: A genotype-first ascertainment of individuals in genomic research allows for a more comprehensive assessment of Mendelian disease and removes biases that confound our understanding of the penetrance and presentation of these conditions.

Humans↗
PubMed2006

Impact of neurofibromatosis 1 on Quality of Life: a cross-sectional study of 176 American cases.

Neurofibromatosis 1 (NF1), a genetic condition most commonly characterized by the presence of dermal neurofibromas and café au lait macules, has a significant impact on Quality of Life (QoL). There is a wide range of phenotypic variability, so that affected individuals may have either medically devastating or relatively mild manifestations that do not impact their daily lives. In this study, the SF-36 and Skindex questionnaires were used to quantitatively investigate the impact of severity and visibility on QoL in an American population. Participants were recruited primarily through advertisements distributed by The Children's Tumor Foundation (CTF). The majority participated by completing a mailed questionnaire in which they rated themselves using Ablon's visibility and Riccardi's severity scales, and then completed the SF-36 and Skindex questionnaires. Participants with NF1 reported a significant impact in all aspects of skin-disease-specific QoL, but the emotional aspect demonstrated the greatest effect. Participants with more visible signs of NF1 reported significantly greater overall effects on their skin-disease-specific QoL than those whose manifestations were more subtle. All domains of general health QoL were affected as well, especially in participants who reported having severe complications. Interestingly, greater visibility was not found to be associated with a significant decrease in general health QoL. These findings are consistent with those found in a French cohort, and demonstrate the utility of incorporating tools designed for use in both the general population and for patients with skin disease in examining the impact of NF1 on QoL.

Adult↗
PubMed2005

The case for strategic international alliances to harness nutritional genomics for public and personal health.

Nutrigenomics is the study of how constituents of the diet interact with genes, and their products, to alter phenotype and, conversely, how genes and their products metabolise these constituents into nutrients, antinutrients, and bioactive compounds. Results from molecular and genetic epidemiological studies indicate that dietary unbalance can alter gene-nutrient interactions in ways that increase the risk of developing chronic disease. The interplay of human genetic variation and environmental factors will make identifying causative genes and nutrients a formidable, but not intractable, challenge. We provide specific recommendations for how to best meet this challenge and discuss the need for new methodologies and the use of comprehensive analyses of nutrient-genotype interactions involving large and diverse populations. The objective of the present paper is to stimulate discourse and collaboration among nutrigenomic researchers and stakeholders, a process that will lead to an increase in global health and wellness by reducing health disparities in developed and developing countries.

Animals↗
PubMed2005

Genetics training in the genomic era.

PURPOSE OF REVIEW: Although major advances have been made in understanding the genetic basis of both rare and common disorders, the number of trainees entering medical genetics in recent years has been dwindling. This review summarizes some possible reasons for this decline and suggests approaches to increase the number of people who enter the field. RECENT FINDINGS: In October 2004 a 'summit meeting' was held at the Banbury Conference Center to discuss the problem. The meeting was attended by leaders in medical genetics from the United States and Canada. Several suggestions were made at the meeting that have resulted in new initiatives to alter medical genetics training and recruit additional trainees. SUMMARY: Major initiatives are being launched that will position medical genetics to work in collaboration with other specialties to lead the integration of genetics into medical practice.

Education, Medical, Continuing↗
PubMed2005

Psychiatric genetics: a survey of psychiatrists' knowledge, opinions, and practice patterns.

OBJECTIVE: Knowledge about the genetic basis of psychiatric illness is growing rapidly, and psychiatrists may be called upon to incorporate this information into clinical practice. The goal of this study was to assess psychiatrists' familiarity with and attitudes toward genetic information. METHOD: We surveyed 844 participants, the majority of whom were psychiatrists, attending a continuing medical education course in the fall of 2002 and measured knowledge, opinions, and current practice patterns in regard to psychiatric genetics. RESULTS: Responses were received from 352 psychiatrists (54% of those surveyed). Most psychiatrists correctly answered fewer than half of survey items assessing general and psychiatric genetic knowledge. While 83% considered it their role to discuss genetic information with patients and families, fewer than 25% felt prepared or competent to do so. In response to hypothetical questions regarding genetic testing, a substantial proportion of psychiatrists indicated willingness to use such tests for diagnostic clarification, as well as presymptomatic and even prenatal risk prediction. The majority of respondents expressed interest in further genetics education. CONCLUSIONS: Our results suggest that psychiatrists view genetic information as clinically relevant, but have limitations in knowledge that may impact the incorporation of psychiatric genetics into clinical practice.

Attitude of Health Personnel↗
PubMed2004

Integration of genetics into medical practice.

It has been a century since the first human genetic disorders were recognized, but only recently have there been any prospects that the genetic approach would become integral to medical practice. Throughout most of the 20th century, medical genetics has focused on rare monogenic and chromosomal disorders. There were major successes, including chromosomal analysis, prenatal diagnosis and newborn screening for inborn errors of metabolism, but the impact was confined to a relatively narrow corner of medicine. The situation has changed, however, with advances in genetics and especially with the sequencing of the human genome. The tools are now at hand to begin to understand the genetic basis of common as well as rare disorders. It is expected that this will lead to major advances in both diagnosis and treatment, so that physicians in all areas of medicine will be using the tools of genetics in their daily practice.

Genetic Diseases, Inborn↗
PubMed2004

The phakomatoses.

The phakomatoses are a diverse set of disorders related principally by a similar tendency to produce patchy manifestations that affect the nervous system and various other tissues. All of the disorders involve the occurrence of benign neoplasms or hamartomatous growths, and all involve the action of a distinct gene that functions as a tumor suppressor. At present, none of the phakomatoses is amenable to effective medical treatment, so management is limited to surveillance and treatment of progressive lesions. The radiologist plays a key role in this management, participating in diagnosis and follow-up of affected patients.

Genes, Tumor Suppressor↗
PubMed2004

Basic genetics.

This article reviews some of the basic principles of genetics to provide a foundation for understanding the application of genetics to medical practice. Definitions of terms that appear here in italics can be found in the on-line, illustrated glossary at www.genetests.org.

Gene Expression↗
PubMed2003

Deletion of the SLUG (SNAI2) gene results in human piebaldism.

Slug is a zinc-finger neural crest transcription factor, encoded by the SLUG gene, which is critical for development of hematopoietic stem cells, germ cells, and melanoblasts in the mouse. In mouse, heterozygous and homozygous slug mutations result in anemia, infertility, white forehead blaze, and depigmentation of the ventral body, tail, and feet. This phenotype is very similar to the heterozygous W (KIT)-mutant mouse phenotype and to human piebaldism, which is characterized by a congenital depigmented patches and poliosis (white forelock). To investigate the possibility that some cases of human piebaldism might result from abnormalities of the human SLUG (SNAI2) gene, we carried out Southern blot analysis of the SLUG gene in 17 unrelated patients with piebaldism, who lack apparent KIT mutations. Three of these patients had evident heterozygous deletions of the SLUG gene encompassing the entire coding region. Real-time PCR confirmed the deletion in all cases. Fluoresence in situ hybridization (FISH) of genomic SLUG probes to metaphase chromosomes independently confirmed the deletion in one of the cases. These findings indicate that some cases of human piebaldism result from mutation of the SLUG gene on chromosome 8, and provide further strong evidence for the role of SLUG in the development of human melanocytes.

Blotting, Southern↗
PubMed2003

Rib defects in patterns of multiple malformations: a retrospective review and phenotypic analysis of 47 cases.

Rib anomalies may occur in isolation, as well as in association with abnormalities of vertebral segmentation and multi-system malformations. Specific entities include the VACTERL and MURCS associations, spondylocostal dysostosis, and spondylothoracic dysostosis. The relative significance of rib anomalies in other lesser known syndromes and associations remains unclear. To document the diagnoses and related defects in patients with rib anomalies as part of broader pattern of anomalies, we retrospectively identified 47 cases from a hospital population, and evaluated specific costal findings and associated birth defects. In our study, fusion was the most common pattern of rib anomaly (72%), followed by bifid (28%) and hypoplastic ribs (26%). Unrecognized patterns of multiple congenital anomalies (MCA) and VACTERL association were the commonest specific diagnoses with a frequency of 30 and 28%, respectively. An associated vertebral defect was found in 72% of the patients. Of those with no vertebral anomaly, the combinations of "rib and cardiac defects alone" and "rib and renal defects alone" were seen in one-third of the patients (4/13). Both the occurrence and type of rib anomaly were helpful in defining certain syndromes and enhanced the likelihood of identifying related malformations.

Abnormalities, Multiple↗
PubMed2003

Human chromosome 7: DNA sequence and biology.

DNA sequence and annotation of the entire human chromosome 7, encompassing nearly 158 million nucleotides of DNA and 1917 gene structures, are presented. To generate a higher order description, additional structural features such as imprinted genes, fragile sites, and segmental duplications were integrated at the level of the DNA sequence with medical genetic data, including 440 chromosome rearrangement breakpoints associated with disease. This approach enabled the discovery of candidate genes for developmental diseases including autism.

Animals↗
PubMed2002

Anaesthetic management of children with tuberous sclerosis.

BACKGROUND: Tuberous sclerosis (TS) is a hamartomatous disease that usually presents with cutaneous and intracranial lesions, but can also affect other organ systems. METHODS: In this report, we retrospectively reviewed the perioperative course of 24 children with TS who had medically intractable seizures as the primary disease process. RESULTS: Cardiac rhabdomyoma was detected in 11 of 18 patients who had a cardiac evaluation, and coexisting congenital heart defects were diagnosed in six. Ten of 17 patients who had a renal evaluation were diagnosed with renal TS, presenting with azotaemia in one and hypertension in four. The major perioperative complications in the 52 anaesthetics, included death (a neonate after cardiac rhabdomyoma resection), seizures (five patients) and bradyarrhythmias (two patients). CONCLUSIONS: Patients with TS and neurological disorders frequently have coexisting cardiac and renal disease as well. Patients with TS should be evaluated for these organ specific disorders prior to surgery.

Adolescent↗
PubMed2002

Clinical features and pathobiology of neurofibromatosis 1.

Neurofibromatosis 1 is a progressive multisystem disorder. The hallmark feature is the occurrence of nerve sheath tumors, neurofibromas. Other features include tumors such as optic gliomas and malignant peripheral nerve sheath tumors. There are also nontumor manifestations, such as skeletal dysplasia and learning disabilities. Since the NF1 gene was identified, much has been learned about the molecular genetics of the disorder; recently, this has led to insights about pathogenesis. Ultimately, it is hoped that this will be translated into specific means of treatment. This review describes the various clinical features of neurofibromatosis 1 and considers them in the context of the pathophysiology of the disorder.

Cell Transformation, Neoplastic↗
PubMed2002

Determination of end points for treatment of neurofibromatosis 1.

Neurofibromatosis 1 is a progressive disorder that affects multiple systems of the body. Management is currently focused on anticipatory guidance, genetic counseling, and symptomatic treatment of specific lesions, usually through surgery. Insights into pathogenesis of the disorder are beginning to suggest possible mechanisms of treatment, and clinical trials have begun for some types of lesions. The unpredictable natural history and variable phenotype present challenges for clinical trials in neurofibromatosis 1, which will need to be addressed to develop a system for reliable testing of potential therapies.

Child↗