RT Book, Section
A1 Kaplan, Josseline
A1 Rozet, Jean-Michel
A1 Perrault, Isabelle
A1 Munnich, Arnold
A2 Valle, David L.
A2 Antonarakis, Stylianos
A2 Ballabio, Andrea
A2 Beaudet, Arthur L.
A2 Mitchell, Grant A.
SR Print(0)
ID 1184070721
T1 Leber Congenital Amaurosis
T2 The Online Metabolic and Molecular Bases of Inherited Disease
YR 2019
FD 2019
PB McGraw-Hill Education
PP New York, NY
SN 9780071459969
LK ommbid.mhmedical.com/content.aspx?aid=1184070721
RD 2024/04/25
AB Leber  congenital  amaurosis  (LCA)  (MIM  204000)  is  characterized  by  severe  or  complete  loss  of  visual  function  apparent  early  in  infancy  with  failure  to  follow  visual  stimuli,  nystagmus,  and  roving  eye  movements.  Affected  individuals  have  an  extinguished  electroretinogram  and  eventually  develop  abnormalities  of  the  ocular  fundus  including  a  pigmentary  retinopathy.  Although  many  LCA  patients  have  no  additional  abnormalities,  in  some  there  is  associated  mental  retardation.  LCA  is  inherited  as  an  autosomal  recessive  trait.  Aside  from  helping  the  patient  adapt  to  life  with  no  visual  function,  there  is  no  treatment.The  LCA  phenotype  is  genetically  heterogeneous,  with  mutations  in  at  least  three  genes  causing  the  disorder.  LCA1  maps  to  17p13  and  encodes  retGC-1,  a  photoreceptor-specific  guanylate  cyclase.  LCA2  maps  to  1p31  and  encodes  RPE65,  a  61-kDa  retinal  pigment  epithelium  (RPE)-specific  microsomal  protein.  Mutations  at  this  locus  also  have  been  shown  to  cause  childhood-onset  severe  retinal  dystrophy  (CSRD).  LCA3  maps  to  19q13.3  and  encodes  CRX,  a  homeodomain  transcription  factor  that  is  a  positive  activator  of  several  photoreceptor-specific  genes.Animal  models  of  LCA  include  the  rd/rd  chick,  in  which  blindness  precedes  photoreceptor  degeneration.  The  responsible  gene  (GC1)  encodes  a  guanylate  cyclase  with  61  percent  amino  acid  identity  to  mammalian  guanylate  cyclase  1,  and  a  deletion/insertion  mutant  allele  has  been  identified  in  the  rd/rd  chick.  Additionally,  a  mouse  model  with  targeted  disruption  of  the  murine  guanylate  cyclase  gene  (GCE)  has  been  produced.  These  mice  exhibit  an  early  loss  of  the  cone  ERG  followed  later  by  loss  of  the  rod  ERG.  Finally,  a  mouse  model  with  targeted  disruption  of  the  RPE65  gene  has  been  produced.  These  animals  have  a  severely  abnormal  dark-adapted  ERG  and  subtle  morphologic  abnormalities  of  the  photoreceptor  outer  segments.