title: A rare transthyretin mutation (Asp18Glu) associated with cardiomyopathy.
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.
authors.affiliation: Department of Biochemistry, Boston University School of Medicine, Amyloid Treatment and Research Program, Boston University School of Medicine, Boston, MA, USA. lconnors@bu.edu
authors.forename: Lawreen Heller
authors.initials: LH
authors.lastname: Connors
authors.forename: Taro
authors.initials: T
authors.lastname: Yamashita
authors.forename: Masahide
authors.initials: M
authors.lastname: Yazaki
authors.forename: Martha
authors.initials: M
authors.lastname: Skinner
authors.forename: Merrill D
authors.initials: MD
authors.lastname: Benson
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics*; D028226:Amyloidosis, Familial / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D001224:Aspartic Acid / Q000235:genetics*; D009202:Cardiomyopathies / Q000097:blood / Q000209:etiology / Q000235:genetics*; D005091:Exons / Q000235:genetics; D018698:Glutamic Acid / Q000235:genetics*; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D018807:Polymorphism, Single-Stranded Conformational; D011228:Prealbumin / Q000032:analysis / Q000235:genetics*
chemical_list: D011228:Prealbumin; D001224:Aspartic Acid; D018698:Glutamic Acid