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D P Judge

Publications and source records attributed to D P Judge.

4 recordsLinked to original sources
PubMed2006

The molecular genetics of Marfan syndrome and related disorders.

Marfan syndrome (MFS), a relatively common autosomal dominant hereditary disorder of connective tissue with prominent manifestations in the skeletal, ocular, and cardiovascular systems, is caused by mutations in the gene for fibrillin-1 (FBN1). The leading cause of premature death in untreated individuals with MFS is acute aortic dissection, which often follows a period of progressive dilatation of the ascending aorta. Recent research on the molecular physiology of fibrillin and the pathophysiology of MFS and related disorders has changed our understanding of this disorder by demonstrating changes in growth factor signalling and in matrix-cell interactions. The purpose of this review is to provide a comprehensive overview of recent advances in the molecular biology of fibrillin and fibrillin-rich microfibrils. Mutations in FBN1 and other genes found in MFS and related disorders will be discussed, and novel concepts concerning the complex and multiple mechanisms of the pathogenesis of MFS will be explained.

Activin Receptors, Type I↗
PubMed2004

Reversible dilated cardiomyopathy associated with glucagonoma.

An association between dilated cardiomyopathy and glucagonoma has not previously been described. A case of a 54 year old woman with tachycardia and congestive heart failure is described. Initial evaluation included an echocardiogram, which showed dilated cardiomyopathy with an ejection fraction of 15%. Coronary angiography and endomyocardial biopsy did not identify a secondary cause of her cardiomyopathy. She subsequently developed necrolytic migratory erythema, and imaging of her pancreas identified a pancreatic mass with a major increase of her serum glucagon concentration. Tachycardia persisted despite treatment with beta blockers. After resection of her tumour, her heart rate normalised and subsequently her heart returned to normal size and function. Glucagon is used to treat overdoses of beta blockers and calcium channel blockers, increasing heart rate by increasing myocardial cyclic AMP concentrations. Although rare, in the appropriate clinical setting, glucagonoma should be considered in the differential diagnosis for tachycardia and dilated cardiomyopathy.

Cardiomyopathy, Dilated↗
PubMed2001

Characterization of microsatellite markers flanking FBN1: utility in the diagnostic evaluation for Marfan syndrome.

Marfan syndrome (MFS) is an autosomal dominant disorder of connective tissue with marked interfamilial and intrafamilial variation in phenotype. The primary defect in affected patients resides in the gene for fibrillin-1 (FBN1) on 15q21. Linkage analysis has shown no locus heterogeneity in the classic phenotype, although substantial allelic heterogeneity exists. Recently it has been shown that the size of the gene is approximately 200 kb. These and other factors have precluded routine mutation screening for presymptomatic and prenatal diagnosis. Previously we described four intragenic microsatellite polymorphisms that can be used for haplotype segregation analysis. The utility of this approach is limited because the markers do not fully span the gene and show incomplete informativeness, with 16% homozygosity for the most common haplotype. We have now identified and localized highly polymorphic microsatellite markers that fall within 1 Mb of FBN1. Complete haplotype heterozygosity was observed in a population of 50 unrelated control individuals when the flanking markers and existing intragenic polymorphisms were used in combination. We demonstrate the utility of haplotype segregation analysis in the presymptomatic diagnosis and counseling of families showing atypical or equivocal manifestations of MFS.

Adult↗