RT Book, Section
A1 Berger, Wolfgang
A1 Ropers, Hans-Hilger
A2 Valle, David L.
A2 Antonarakis, Stylianos
A2 Ballabio, Andrea
A2 Beaudet, Arthur L.
A2 Mitchell, Grant A.
SR Print(0)
ID 1184070947
T1 Norrie Disease
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=1184070947
RD 2024/04/16
AB Norrie  disease  (ND)  (MIM  310600)  is  a  severe  form  of  congenital  blindness  characterized  by  degenerative  and  proliferative  changes  in  the  neuroretina  and  vitreous  followed  by  progressive  atrophy  of  the  eyes.Leukokoria,  due  to  retrolental  structures  and  retinal  detachment,  can  be  recognized  shortly  after  birth.  Other  ocular  hallmarks  of  ND  are  persistent  hyperplastic  primary  vitreous,  hyaloid  vessels,  shallow  anterior  chamber,  and  vitreoretinal  hemorrhages.One-third  of  patients  are  mentally  retarded  and  develop  sensorineural  deafness.  Occasionally,  other  clinical  features  are  seen,  including  hypogonadism  and  microcephaly,  some  of  which  may  be  due  to  defects  extending  to  neighboring  genes.The  disease  is  inherited  as  an  X-linked  recessive  trait.  Male-to-male  transmission  has  been  excluded,  and  carrier  females  are  usually  healthy.Linkage  and  deletion  mapping  studies  have  assigned  the  ND  locus  to  a  600-kb  segment  of  the  Xp11.3-p11.4  interval  and  paved  the  way  for  its  isolation  by  positional  cloning.The  gene  encodes  a  133-amino-acid  polypeptide  with  an  N-terminal  signal  sequence  and  a  C-terminal  cysteine-knot  motif.  It  shows  homology  with  proteins  involved  in  cell  interaction  and  differentiation  processes.  Computer  modeling  and  expression  studies  suggest  the  formation  of  homodimers  via  the  C-terminal  Cys-knot.So  far  mutations  have  been  described  in  more  than  90  patients  with  ND.  Missense  mutations  are  the  most  frequent  (50  percent),  followed  by  deletions  (15–20  percent)  and  nonsense  mutations  (13  percent).  Mutations  in  this  gene  can  give  rise  to  three  clinically  distinct  phenotypes,  i.e.,  ND,  exudative  vitreoretinopathy  (EVR)  (MIM  143200),  and  retinopathy  of  prematurity  (ROP).A  mouse  mutant  lacking  the  N-terminal  portion  of  the  ND  gene  was  generated  by  gene  targeting.  Mutant  mice  show  histologic  and  pyhsiologic  changes  in  the  innermost  layers  of  the  retina,  including  the  ganglion  and  nerve  fiber  layers.