A rare transthyretin mutation (Asp18Glu) associated with cardiomyopathy

Lawreen Heller Connors, Taro Yamashita, Masahide Yazaki, Martha Skinner, Merrill Benson

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The identification of a rare transthyretin (TTR) gene mutation (Asp18Glu) in a middle-aged male with biopsy proven amyloid disease featuring cardiomyopathy is described. The more commonly occurring light chain amyloidosis (AL) was initially considered, but negative hematologic testing prompted screening for a pathologic TTR mutation. A differential diagnosis of familial transthyretin type amyloidosis (ATTR) was established using a combination of molecular genetic and biochemical techniques. Single-strand conformation polymorphism (SSCP) screening of exons 2, 3 and 4 of the TTR gene indicated the presence of atypical DNA. SSCP testing was performed using a new non-radioactive, silver stained minigel technique. The genetic abnormality was identified by direct DNA sequence analysis as a T to A transversion at the third base position in codon 18. This result was confirmed by restriction fragment length polymorphism (RFLP) testing. The presence of the variant protein, TTR Asp18Glu, in serum from the proband was confirmed by mass spectrometric analysis.

Original languageEnglish
Pages (from-to)61-66
Number of pages6
JournalAmyloid
Volume11
Issue number1
DOIs
StatePublished - Mar 2004

Fingerprint

Prealbumin
Cardiomyopathies
Mutation
Familial Amyloidosis
Genetic Techniques
Amyloidosis
DNA Sequence Analysis
Silver
Amyloid
Codon
Restriction Fragment Length Polymorphisms
Genes
Molecular Biology
Exons
Differential Diagnosis
Biopsy
Light
DNA
Serum
Proteins

Keywords

  • Cardiomyapathy
  • Familial amyloidosis
  • Mutation
  • Transthyretin

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medicine(all)

Cite this

A rare transthyretin mutation (Asp18Glu) associated with cardiomyopathy. / Connors, Lawreen Heller; Yamashita, Taro; Yazaki, Masahide; Skinner, Martha; Benson, Merrill.

In: Amyloid, Vol. 11, No. 1, 03.2004, p. 61-66.

Research output: Contribution to journalArticle

Connors, Lawreen Heller ; Yamashita, Taro ; Yazaki, Masahide ; Skinner, Martha ; Benson, Merrill. / A rare transthyretin mutation (Asp18Glu) associated with cardiomyopathy. In: Amyloid. 2004 ; Vol. 11, No. 1. pp. 61-66.
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