Showing papers by "Martha Skinner published in 2008"
TL;DR: A proteomics methodology utilizing two-dimensional polyacrylamide gel electrophoresis followed by matrix-assisted laser desorption/ionization mass spectrometry and peptide mass fingerprinting to directly characterize amyloid deposits in abdominal subcutaneous fat obtained by fine needle aspiration from patients diagnosed as having amyloidsoses typed as immunoglobulin light chain or transthyretin is developed.
130 citations
TL;DR: This case series reports 4 patients with cardiac light-chain amyloidosis and left ventricular outflow tract obstruction at rest, suggesting that there may be echocardiographic overlap between these 2 disparate disease processes.
Abstract: Hypertrophic cardiomyopathy and cardiac amyloidosis result in thickening of the left ventricle, as visualized by 2-dimensional echocardiography. Hemodynamically, hypertrophic cardiomyopathy can be typified by a left ventricular outflow tract gradient and systolic anterior motion of the mitral apparatus, findings rarely seen in cardiac amyloidosis. This case series reports 4 patients with cardiac light-chain amyloidosis and left ventricular outflow tract obstruction at rest, suggesting that there may be echocardiographic overlap between these 2 disparate disease processes. In a series of consecutive patients with cardiac light-chain amyloidosis over a 2-year period, the prevalence of these echocardiographic findings was approximately 4%. In conclusion, awareness of this overlap in echocardiographic presentation may permit more accurate diagnosis, particularly at early stages of amyloid disease, when more treatment options exist.
34 citations
TL;DR: A new transthyretin position 30 mutation (alanine for valine) in a family of German descent is observed in patients with familial amyloid polyneuropathy.
Abstract: Jones LA, Skare JC, Cohen AS, Harding JA, Milunsky A, Skinner M. Familial amyloid polyneuropathy: a new transthyretin position 30 mutation (alanine for valine) in a family of German descent. Clin Genet 1992:41: 70–73.
Familial amyloidotic polyneuropathy (FAP) is a dominantly inherited form of amyloidosis usually associated with an abnormal transthyretin (TTR), previously known as prealbumin. Several disease-related variants of the protein, each with a different amino acid substitution and correlating DNA point mutation, have been identified. The TTR gene from a patient suffering from this disorder was asymmetrically amplified and directly sequenced, revealing a cytosine for thymine substitution in the second base of codon 30 and the creation of a novel Cfo I restriction endo-nuclease site in exon 2. This mutation results in a previously undescribed substitution of an alanine for valine in the final TTR protein. Analysis of the amino acid mutation reveals it to be a hydrophilic substitution at a hydrophobic core position. Alanine at position 30 represents the second FAP-associated mutation at position 30 in TTR.
29 citations
TL;DR: The discovery of this mutation suggests that intermolecular binding between hydrophobic polypeptide loops on the surface of transthyretin can lead to familial amyloidotic polyneuropathy.
Abstract: A new transthyretin variant which lost an Sph I cleavage site within exon 3 has been characterized. A 260 bp sequence containing exon 3 was amplified using the polymerase chain reaction, and the variant was found to possess a Bsm I cleavage site not present in normal transthyretin. This led to the conclusion that the histidine at position 90 was replaced by asparagine, and amino acid analysis supported the conclusion. The discovery of this mutation suggests that intermolecular binding between hydrophobic polypeptide loops on the surface of transthyretin can lead to familial amyloidotic polyneuropathy.
22 citations
TL;DR: It is concluded that his90asn is a nonpathogenic variant of transthyretin that has already been seen in Japanese FAP patients and has been found in Portuguese and German individuals without FAP.
Abstract: A family with familial amyloidotic polyneuropathy (FAP) was previously found to have a substitution of asparagine for histidine at position 90 of transthyretin. Members with his90asn developed FAP. However, close examination of the transthyretin gene revealed that glu42gly is coinheri-ted with his90asn in this family. Since glu42gly has already been seen in Japanese FAP patients, and his90asn has been found in Portuguese and German individuals without FAP, we conclude that his90asn is a nonpathogenic variant.
18 citations
TL;DR: It is suggested that an as yet unknown post‐translational modification may have occurred in the FAP‐associated Asn 90 variant, turning it into an amyloidogenic molecule.
Abstract: Recently, a new transthyretin (TTR) variant was described in the normal Portuguese and German populations. The same substitution was found associated with familial amyloidotic polyneuropathy (FAP) in an American family of Italian origin. Comparative isoelectric focusing studies showed a difference in the mobility pattern between the non-pathogenic and pathogenic variants. However, comparative DNA sequencing between them did not reveal any additional mutation. Comparative isoelectric focusing between the variants and TTR Asn 90 produced by recombinant techniques indicated that the non-pathogenic variant has the electrophoretic behaviour expected for the mutation. We suggest that an as yet unknown post-translational modification may have occurred in the FAP-associated Asn 90 variant, turning it into an amyloidogenic molecule.
8 citations
TL;DR: This data indicates that LV morphologic differences between types of amyloidosis are lacklustre, and the need for further research into this topic is urgently needed.
Abstract: Background: Cardiac amyloidosis is generally described as a disease with left ventricular (LV) wall thickening, but data supporting LV morphologic differences between types of amyloidosis are lacki...
2 citations