TY  - CHAP
M1  - Book, Section
TI  - Amyloidosis
A1  - Benson, Merrill D.
A2  - Valle, David L.
A2  - Antonarakis, Stylianos
A2  - Ballabio, Andrea
A2  - Beaudet, Arthur L.
A2  - Mitchell, Grant A.
PY  - 2019
T2  - The Online Metabolic and Molecular Bases of Inherited Disease
AB  - Hereditary  amyloidosis  is  characterized  by  the  extracellular  accumulation  of  protein  fibrils  having  β-pleated  sheet  structure.  Actually,  hereditary  amyloidosis  is  only  one  of  a  number  of  forms  of  amyloidosis,  each  characterized  by  the  protein  that  is  the  basic  subunit  of  the  amyloid  fibril.  Systemic  hereditary  amyloidosis  (involving  multiple  organ  systems)  may  be  associated  with  variant  forms  of  transthyretin,  apolipoprotein  A-I,  gelsolin,  cystatin  C,  fibrinogen,  or  lysozyme.  Other  forms  of  systemic  amyloidosis,  which  are  not  hereditary,  include  immunoglobulin  (amyloidosis  of  light  chain  (AL),  primary)  amyloidosis,  in  which  the  subunit  protein  is  the  variable  portion  of  monoclonal  immunoglobulin  light  chain;  reactive  (secondary)  amyloidosis,  in  which  the  subunit  protein  is  a  degradation  product—amyloid  A  (AA)—of  a  serum  acute-phase  protein—serum  amyloid  A  (SAA);  and  β2-microglobulin  (dialysis-associated)  amyloidosis,  in  which  the  subunit  protein  is  β2-microglobulin.  All  forms  of  amyloidosis  cause  illness  and  death  by  physical  encroachment  of  the  deposits  on  normal  organ  structures.  In  autosomal  dominant  hereditary  amyloidosis,  peripheral  neuropathy  is  the  most  common  finding,  although  infiltration  of  vital  organs,  such  as  heart,  kidney,  and  bowel,  give  various  syndromes,  which  usually  lead  to  death.Hereditary  amyloidosis  is  a  late-onset  disease  with  clinical  symptoms  beginning  in  most  kindreds  within  the  third  to  seventh  decades  of  life.  The  clinical  disease  usually  progresses  over  5  to  15  years  and  ends  with  death  from  cardiac  failure,  renal  failure,  or  malnutrition.  In  some  kindreds,  heterozygotes  with  late-onset  disease,  however,  have  lived  past  age  90.  Gene  prevalence  is  not  known,  because  there  are  a  number  of  mutations  in  the  genes  for  various  plasma  proteins,  and  many  of  the  kindreds  were  characterized  only  recently.  In  the  United  States,  the  prevalence  of  variant  transthyretin  genes  associated  with  amyloidosis  varies  with  ethnic  origin.  In  Caucasians,  the  prevalence  is  relatively  low  (perhaps  1  in  100,000).  In  Americans  of  African  descent,  as  many  as  1  in  25  may  have  one  specific  transthyretin  variant  (Val122Ile)  that  causes  late-onset  cardiomyopathy.The  primary  defect  in  autosomal  dominant  transthyretin  amyloidosis  results  from  one  of  a  number  of  mutations  in  the  gene  for  transthyretin,  which  is  a  single-copy  sequence  on  chromosome  18.  To  date,  73  single  amino  acid  substitutions  in  the  transthyretin  molecule  that  could  be  associated  with  hereditary  amyloidosis  have  been  found.  In  addition,  six  mutations  have  been  described  in  apolipoprotein  A-I,  two  in  gelsolin,  four  in  fibrinogen  A  α-chain,  two  in  lysozyme,  and  one  in  cystatin  C,  all  of  which  are  associated  with  systemic  amyloidosis.Direct  DNA  tests  have  been  developed  for  many  of  the  variant  genes  for  transthyretin,  apolipoprotein  A-I,  gelsolin,  fibrinogen,  lysozyme,  and  cystatin  C.  In  addition,  modern  molecular  biology  techniques  can  provide  easy  detection  methods  for  all  of  the  demonstrated  mutations.  In  many  cases,  restriction  enzyme  analysis  of  PCR  amplification  products  has  replaced  Southern  blot  analysis.  Direct  DNA  sequencing  based  on  PCR  technology  is  used  in  the  discovery  of  new  mutations.  DNA  tests  have  been  established  for  certain  protein  variants,  and  these  are  used  for  genetic  counseling.Prenatal  diagnosis  has  been  developed  for  at  least  two  forms  of  transthyretin  amyloidosis  based  on  PCR  technology.Autosomal  dominant  forms  of  amyloidosis  that  are  localized  to  one  ...
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
Y2  - 2024/04/18
UR  - ommbid.mhmedical.com/content.aspx?aid=1181476094
ER  -