PMID- 10595931
OWN - NLM
STAT- MEDLINE
DCOM- 19991228
LR  - 20190607
IS  - 0002-9440 (Print)
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Linking)
VI  - 155
IP  - 6
DP  - 1999 Dec
TI  - Somatic mutations of the L12a gene in V-kappa(1) light chain deposition disease: 
      potential effects on aberrant protein conformation and deposition.
PG  - 2009-17
AB  - Light chain deposition disease (LCDD) and light chain amyloidosis (AL) are 
      disorders of monoclonal immunoglobulin deposition in which normally soluble serum 
      precursors form insoluble deposits in tissues. A common feature in both is the 
      clonal proliferation of B-cells that produce pathogenic light chains. However, 
      the deposits in LCDD differ from those in AL in that they are ultrastructurally 
      granular rather than fibrillar and do not bind Congo red or colocalize with 
      amyloid P component or apolipoprotein E. The reason(s) for their differences are 
      unknown but are likely multifactorial and related to their protein conformation 
      and their interaction with other molecules and tissue factors in the 
      microenvironment. Knowledge of the primary structure of the light chains in LCDD 
      is very limited. In the present study two new kappa(1) light chains from patients 
      with LCDD are described and compared to seven other reported kappa-LCDD proteins. 
      The N-terminal amino acid sequences of light chain GLA extracted from the renal 
      biopsy and light chain CHO from myocardial tissue were each identical to the 
      respective light chains isolated from the urines and to the V-region amino acid 
      sequences translated from the cloned cDNAs obtained from bone marrow cells. The 
      germline V-region sequences, determined from the genomic DNA in both and in MCM, 
      a previously reported kappa(1) LCDD light chain, were identical and related to 
      the L12a germline gene. The expressed light chains in all three exhibit amino 
      acid substitutions that arise from somatic mutation and result in increased 
      hydrophobicity with the potential for protein destabilization and disordered 
      conformation.
FAU - Vidal, R
AU  - Vidal R
AD  - Department of Pathology, New York University School of Medicine, New York, New 
      York, USA.
FAU - Goni, F
AU  - Goni F
FAU - Stevens, F
AU  - Stevens F
FAU - Aucouturier, P
AU  - Aucouturier P
FAU - Kumar, A
AU  - Kumar A
FAU - Frangione, B
AU  - Frangione B
FAU - Ghiso, J
AU  - Ghiso J
FAU - Gallo, G
AU  - Gallo G
LA  - eng
GR  - R01 AR002594/AR/NIAMS NIH HHS/United States
GR  - AR 02594/AR/NIAMS NIH HHS/United States
GR  - DKY 3757/DK/NIDDK NIH HHS/United States
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (Immunoglobulin Light Chains)
RN  - 0 (Immunoglobulin kappa-Chains)
SB  - IM
MH  - Amino Acid Sequence
MH  - Base Sequence
MH  - Blotting, Western
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Female
MH  - Humans
MH  - Immunoglobulin Light Chains/chemistry/*metabolism
MH  - Immunoglobulin kappa-Chains/chemistry/metabolism
MH  - Immunohistochemistry
MH  - Isoelectric Point
MH  - Kidney Diseases/*metabolism/pathology
MH  - Middle Aged
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Paraproteinemias/*metabolism/pathology/urine
MH  - Protein Conformation
MH  - Sequence Analysis, DNA
PMC - PMC1866929
EDAT- 1999/12/14 00:00
MHDA- 1999/12/14 00:01
PMCR- 2000/06/01
CRDT- 1999/12/14 00:00
PHST- 1999/12/14 00:00 [pubmed]
PHST- 1999/12/14 00:01 [medline]
PHST- 1999/12/14 00:00 [entrez]
PHST- 2000/06/01 00:00 [pmc-release]
AID - S0002-9440(10)65520-4 [pii]
AID - 1986 [pii]
AID - 10.1016/s0002-9440(10)65520-4 [doi]
PST - ppublish
SO  - Am J Pathol. 1999 Dec;155(6):2009-17. doi: 10.1016/s0002-9440(10)65520-4.