Victor A. McKusick

Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders

Online Mendelian Inheritance in Man (OMIM) is a comprehensive, authoritative and timely knowledgebase of human genes and genetic disorders compiled to support research and education in human genomics and the practice of clinical genetics. Started by Dr Victor A. McKusick as the definitive reference Mendelian Inheritance in Man, OMIM (www.ncbi.nlm.nih.gov/omim) is now distributed electronically by the National Center for Biotechnology Information (NCBI), where it is integrated with the Entrez suite of databases. Derived from the biomedical literature, OMIM is written and edited at Johns Hopkins University with input from scientists and physicians around the world. Each OMIM entry has a full-text summary of a genetically determined phenotype and/or gene and has numerous links to other genetic databases such as DNA and protein sequence, PubMed references, general and locus-specific mutation databases, approved gene nomenclature, and the highly detailed mapviewer, as well as patient support groups and many others. OMIM is an easy and straightforward portal to the burgeoning information in human genetics.

Online Mendelian Inheritance In Man (OMIM)

Online Mendelian Inheritance In Man (OMIM) is a public database of bibliographic information about human genes and genetic disorders. Begun by Dr. Victor McKusick as the authoritative reference Mendelian Inheritance in Man, it is now distributed electronically by the National Center for Biotechnology Information (NCBI). Material in OMIM is derived from the biomedical literature and is written by Dr. McKusick and his colleagues at Johns Hopkins University and elsewhere. Each OMIM entry has a full text summary of a genetic phenotype and/or gene and has copious links to other genetic resources such as DNA and protein sequence, PubMed references, mutation databases, approved gene nomenclature, and more. In addition, NCBIs neighboring feature allows users to identify related articles from PubMed selected on the basis of key words in the OMIM entry. Through its many features, OMIM is increasingly becoming a major gateway for clinicians, students, and basic researchers to the ever‐growing literature and resources of human genetics. Hum Mutat 15:57–61, 2000.

The Marfan Syndrome: Diagnosis and Management

THE Marfan syndrome is classified as a heritable disorder of connective tissue because clinical and pathological alterations involve supporting elements. It long has been assumed that an inborn err...

Life Expectancy and Causes of Death in the Marfan Syndrome

Abstract The Marfan syndrome is a dominantly inherited disorder of connective tissue with multisystem involvement. The cardiac complications, particularly aortic dilatation, dissection and rupture ...

Mendelian Inheritance in Man and Its Online Version, OMIM

Last year marked the 40th anniversary of the publication of the first print edition of Mendelian Inheritance in Man (MIM).1 This seems an appropriate juncture at which to review its origins, evolution, and present status, including and particularly those of its online version, OMIM (Online Mendelian Inheritance in Man). This is an opportunity, at the same time, to review in brief the rapid progress in an important part of medical genetics and genomics, as chronicled in MIM/OMIM over these 40 years, and to contemplate the future challenges of OMIM.

The Cardiovascular Aspects of Marfan's Syndrome: A Heritable Disorder of Connective Tissue

Clinically, Marfans disease behaves as an abiotrophy of some connective tissue element. Cardiovascular manifestations result from defective aortic media, defective valve cusps, interatrial communication, and pectus excavatum. The defect of the aortic media manifests itself by dissecting aneurysm, diffuse aneurysm of the ascending aorta or a combination. Subacute bacterial endocarditis in a patient with Marfans disease is described. Interatrial septal defect is less frequent than previously believed. Cardiac symptoms in severe pectus excavatum must be evaluated in light of possible Marfans disease. Fifty families in which at least one bona fide instance of Marfans disease has occurred were collected.

Defect in Conversion of Procollagen to Collagen in a Form of Ehlers-Danlos Syndrome

Three patients with a form of the Ehlers-Danlos syndrome, a generalized disorder of connective tissue, have detectable amounts of procollagen in extracts of their skin and tendon. The activity of procollagen peptidase, the enzyme that converts procollagen to collagen, is reduced in cultures of fibroblasts. The clinical manifestations of this syndrome may be related to impaired enzymatic conversion of procollagen to collagen. Cultures of skin fibroblasts from these patients have an increased rate of synthesis of collagenous protein (collagen and procollagen), possibly related to the inability of these cells to convert procollagen to collagen.

Classification of pseudoxanthoma elasticum: Report of a consensus conference

Pseudoxanthoma elasticum (PXE) is inherited through both autosomal recessive and autosomal dominant pathways. The seminal pathophysiologic event is an aberrant calcification of elastic fibers in the skin, retina, and cardiovascular systems. Characteristicclinical pathologic events occurin eachof these areasas thedisorderprogresses throughout the lifetime of an affected person. The disorder is also characterized by marked clinical heterogeneity. In 1975, PopeI postulated, on the basis of a Britishstudyof 120patients,the existenceoftwodistinct autosomaldominantand twodistinctautosomal recessive phenotypes. Autosomal dominant inheritance was found in approximately 50% of the patients. Sincethen,Neldner.i onthe basisofa 20-year study of 100 patients in the United States, has reported that 90% of his patients appear to have an autosomal recessive inheritance pattern and that it was impossible to separate the group into subtypes based on the phenotype. In brief, with time all patients tend to merge into a single classic phenotype involving the skin, eyes, and cardiovascular system, but with considerable variation in expression of the disorder. The description ofpatients withocularandhistopathologicmanifestations of PXE in the absence of

Surgical treatment of aneurysms of the ascending aorta in the Marfan syndrome. Results of composite-graft repair in 50 patients

The life expectancy of patients with the Marfan syndrome is reduced by complications caused by dilatation of the ascending aorta. Because surgical therapy with a composite graft may alter this natural history, we analyzed the preoperative and long-term postoperative status of 50 consecutive patients who received such a graft. At surgery, the patients had a mean age of 32.2 years and a mean aortic diameter of 7.1 cm (range, 5.3 to 10). Dissection of the ascending aorta was present in 14 patients and was acute in 5. None of the 44 patients who underwent elective repair, and only one of the six patients who had emergency surgery, died in the hospital; thus, the overall hospital mortality was 2 percent. Five of the 49 survivors died during a follow-up period of up to eight years (10.2 percent late mortality). During the most recent four years of evaluation of this series (38 patients), no postoperative deaths due to intrathoracic problems occurred. Actuarial survival was 87 percent at both two and five years. Composite-graft repair of the ascending aorta in patients with the Marfan syndrome can be performed with low operative and long-term mortality. Because of the unfavorable natural history of the Marfan syndrome and the potential for dissection in moderately dilated aortic roots, we recommend prophylactic repair when the aneurysm reaches a diameter of 6 cm.

Aortic root replacement. Risk factor analysis of a seventeen-year experience with 270 patients.

Between September 1976 and September 1993, 270 patients underwent aortic root replacement at our institution. Two hundred fifty-two patients underwent a Bentall composite graft repair and 18 patients received a cryopreserved homograft aortic root. One hundred eighty-seven patients had a Marfan aneurysm of the ascending aorta (41 with dissection) and 53 patients had an aneurysm resulting from nonspecific medial degeneration (17 with dissection). These 240 patients were considered to have annuloaortic ectasia. Thirty patients were operated on for miscellaneous lesions of the aortic root. Thirty-day mortality for the overall series of 270 patients was 4.8% (13/270). There was no 30-day mortality among 182 patients undergoing elective root replacement for annuloaortic ectasia without dissection. Thirty-six of the 270 patients having root replacement also had mitral valve operations. There was no hospital mortality for aortic root replacement in these 36 patients, but there were seven late deaths. Twenty-two patients received a cryopreserved homograft aortic root; 18 of these were primary root replacements and four were repeat root replacements for late endocarditis. One early death and two late deaths occurred in this group. Actuarial survival for the overall group of 270 patients was 73% at 10 years. In a multivariate analysis, only poor New Year Heart Association class (III and IV), non-Marfan status, preoperative dissection, and male gender emerged as significant predictors of early or late death. Endocarditis was the most common late complication (14 of 256 hospital survivors) and was optimally treated by root replacement with a cryopreserved aortic homograft. Late problems with the part of the aorta not operated on occur with moderate frequency; careful follow-up of the distal aorta is critical to long-term survival.