PMID- 10487826
OWN - NLM
STAT- MEDLINE
DCOM- 19991007
LR  - 20220310
IS  - 0002-9440 (Print)
IS  - 0002-9440 (Linking)
VI  - 155
IP  - 3
DP  - 1999 Sep
TI  - The new apolipoprotein A-I variant leu(174) --> Ser causes hereditary cardiac
      amyloidosis, and the amyloid fibrils are constituted by the 93-residue N-terminal
      polypeptide.
PG  - 695-702
AB  - We identified a novel missense mutation in the apolipoprotein A-I gene, T2069C
      Leu(174) --> Ser, in a patient affected by familial systemic nonneuropathic
      amyloidosis. The amyloid deposits mostly affected the heart of the proband, who
      underwent transplantation for end-stage congestive heart failure. Amyloid fibrils
      of myocardial and periumbilical fat samples immunoreacted exclusively with
      anti-ApoA-I antibodies. Amyloid fibrils extracted from the heart were
      constituted, according to amino acid sequencing and mass spectrometry analysis,
      by an amino-terminal polypeptide ending at Val(93) of apolipoprotein A-I
      (apoA-I); no other significant fragments were detected. The mutation segregates
      with the disease; it was demonstrated in the proband and in an affected uncle and
      excluded in three healthy siblings. The plasma levels of high-density lipoprotein
      and apoA-I were significantly lower in the patient than in unaffected
      individuals. This represents the first case of familial apoA-I amyloidosis in
      which the mutation is outside the polypeptide fragment deposited as fibrils.
      Visualization of the mutation in the three-dimensional structure of lipid-free
      apoA-I, composed of four identical polypeptide chains, indicates that position
      174 of one chain is located near position 93 of an adjacent chain and suggests
      that the amino acid replacement in position 174 is permissive for a proteolytic
      split at the C-terminal of Val(93).
FAU - Obici, L
AU  - Obici L
AD  - Biotechnology Research Laboratories, Institute of Human Pathology, Division of
      Cardiology, IRCCS Policlinico San Matteo, Pavia, Italy.
FAU - Bellotti, V
AU  - Bellotti V
FAU - Mangione, P
AU  - Mangione P
FAU - Stoppini, M
AU  - Stoppini M
FAU - Arbustini, E
AU  - Arbustini E
FAU - Verga, L
AU  - Verga L
FAU - Zorzoli, I
AU  - Zorzoli I
FAU - Anesi, E
AU  - Anesi E
FAU - Zanotti, G
AU  - Zanotti G
FAU - Campana, C
AU  - Campana C
FAU - Vigano, M
AU  - Vigano M
FAU - Merlini, G
AU  - Merlini G
LA  - eng
GR  - E.0793/TI_/Telethon/Italy
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (Amyloid)
RN  - 0 (Apolipoprotein A-I)
RN  - 0 (Peptide Fragments)
SB  - IM
MH  - Amino Acid Substitution
MH  - Amyloid/*chemistry/ultrastructure
MH  - Amyloidosis/complications/*genetics
MH  - Apolipoprotein A-I/chemistry/*genetics
MH  - Chromatography, Gel
MH  - Heart Diseases/*etiology
MH  - Humans
MH  - Male
MH  - Mass Spectrometry
MH  - Middle Aged
MH  - Models, Molecular
MH  - Molecular Weight
MH  - Myocardium/chemistry/ultrastructure
MH  - Peptide Fragments/*chemistry/ultrastructure
MH  - Point Mutation/genetics
MH  - Polymerase Chain Reaction
MH  - Sequence Analysis, DNA
PMC - PMC1866882
EDAT- 1999/09/17 00:00
MHDA- 1999/09/17 00:01
CRDT- 1999/09/17 00:00
PHST- 1999/09/17 00:00 [pubmed]
PHST- 1999/09/17 00:01 [medline]
PHST- 1999/09/17 00:00 [entrez]
AID - S0002-9440(10)65167-X [pii]
AID - 10.1016/S0002-9440(10)65167-X [doi]
PST - ppublish
SO  - Am J Pathol. 1999 Sep;155(3):695-702. doi: 10.1016/S0002-9440(10)65167-X.