TY  - CHAP
M1  - Book, Section
TI  - Charcot-Marie-Tooth Peripheral Neuropathies and Related Disorders
A1  - Lupski, James R.
A1  - Garcia, Carlos A.
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  - Charcot-Marie-Tooth  (CMT)  (MIM  118220)  polyneuropathy  syndrome  represents  a  clinically  and  genetically  heterogeneous  group  of  disorders  of  the  peripheral  nerve.  Two  major  types  are  distinguished  by  measuring  motor  nerve  conduction  velocities  (NCV).  CMT1  is  a  demyelinating  neuropathy  characterized  by  symmetrically  slowed  motor  NCV  (usually  85  percent  of  patients  with  HNPP.  The  CMT1A  duplication  and  HNPP  deletion  result  from  unequal  crossing  over  and  reciprocal  homologous  recombination  involving  a  24-kb  repeat—CMT1A  region-specific  low-copy  repeats  (CMT1A-REP)—that  flanks  the  1.5-Mb  region.  A  meiotic  recombination  hotspot  occurs  within  CMT1A-REP.  The  majority  of  the  de  novo  duplication  and  deletion  events  occur  in  meiosis  of  the  male  germ  cells.The  CMT1A  and  HNPP  phenotypes  result  from  a  gene  dosage  effect.  CMT1A  is  due  to  trisomic  overexpression  of  the  peripheral  myelin  protein-22  gene  (PMP22)whereas  HNPP  results  from  monosomic  underexpression  of  PMP22.  In  rare  patients  without  the  CMT1A  duplication  or  HNPP  deletion,  PMP22  point  mutations  can  cause  disease.  Null  alleles  or  haploinsufficiency  cause  HNPP,  while  gain-of-function  or  dominant-negative  missense  amino  acid  substitution  results  in  CMT1A  or  DSS.Mutations  in  myelin  protein  zero  (MPZ),  connexin  32  (Cx32)or  gap  junction  protein  β1  (GJB1),  and  early  growth  response  2  (EGR2,  the  human  Krox-20  homologue)  genes  can  also  cause  CMT1  (MPZ,  Cx32,  EGR2),  DSS  (MPZ,  EGR2),  or  CHN  (MPZ,  ...
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
Y2  - 2024/04/16
UR  - ommbid.mhmedical.com/content.aspx?aid=1181479189
ER  -