Document Detail


New transthyretin mutation V28M in a Portuguese kindred with amyloid polyneuropathy.
MedLine Citation:
PMID:  10882995     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A 62-year-old Portuguese man, with no history of familial amyloid polyneuropathy (FAP), and a 2(1/2)-year history of tingling in the toes and sexual dysfunction was found neurophysiologically to have a sensory-motor axonal polyneuropathy. Autonomic tests showed slight sympathetic and marked parasympathetic involvement. Heart, kidney, and eyes were normal. Single strand conformation polymorphism (SSCP) mutation analysis for the transthyretin (TTR) gene was performed. The SSCP pattern suggested the presence of a mutation in exon 2, but was different from the pattern observed for a control representing the most common TTR mutation associated with FAP, i.e., TTR V30M. DNA sequencing analysis revealed an A-to-G transition in the first base of codon 28 normally encoding a valine, giving rise to a methionine residue. The presence of this extra methionine was confirmed by peptide mapping and mass spectrometry analysis. Biopsy of nerve and skin of the propositus showed amyloid deposits that were immunoreactive for TTR. This is a new variant TTR related to late-onset amyloid neuropathy with autonomic dysfunction. This case confirms that TTR mutation screening should be considered in patients with a clinical disorder consistent with amyloid neuropathy even in the absence of a family history.
Authors:
M de Carvalho; P Moreira; T Evangelista; J L Ducla-Soares; M Bento; R Fernandes; M J Saraiva
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Publication Detail:
Type:  Case Reports; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Muscle & nerve     Volume:  23     ISSN:  0148-639X     ISO Abbreviation:  Muscle Nerve     Publication Date:  2000 Jul 
Date Detail:
Created Date:  2000-08-07     Completed Date:  2000-08-07     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7803146     Medline TA:  Muscle Nerve     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1016-21     Citation Subset:  IM    
Copyright Information:
Copyright 2000 John Wiley & Sons, Inc.
Affiliation:
Department of Neurology, Hospital de Santa Maria, Lisbon, and EMG Laboratory, Centro de Estudos Egas Moniz, Lisbon, Portugal.
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MeSH Terms
Descriptor/Qualifier:
Adult
Amyloid Neuropathies / genetics*,  pathology
Autonomic Nervous System / physiopathology
Axons / pathology
Blood Pressure / physiology
Electromyography
Exons / genetics
Humans
Immunohistochemistry
Male
Mutation / genetics*,  physiology
Polymorphism, Single-Stranded Conformational
Portugal
Prealbumin / chemistry,  genetics*
Reverse Transcriptase Polymerase Chain Reaction
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Sural Nerve / pathology
Sympathetic Nervous System / physiopathology
Chemical
Reg. No./Substance:
0/Prealbumin

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