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J Med Genet 39:e66 doi:10.1136/jmg.39.10.e66
  • Online mutation report

Novel homozygous mutation in the alpha subunit of the rod cGMP gated channel (CNGA1) in two Spanish sibs affected with autosomal recessive retinitis pigmentosa

  1. E Paloma1,
  2. A Martínez-Mir1,*,
  3. B García-Sandoval2,
  4. C Ayuso2,
  5. L Vilageliu1,
  6. R Gonzàlez-Duarte1,
  7. S Balcells1
  1. 1Departament de Genética, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain
  2. 2Departamento de Genética, Fundación Jiménez-Díaz, Madrid, Spain
  1. Correspondence to:
 Dr S Balcells, Departament de Genética, Universitat de Barcelona, Av Diagonal 645, E-08028 Barcelona, Spain;
 susan{at}porthos.bio.ub.es

    Retinitis pigmentosa (RP, MIM 268000) comprises a clinically and genetically heterogeneous group of disorders leading to progressive dysfunction of the rod photoreceptors of the retina. Patients suffer early night blindness followed by loss of peripheral vision associated with pigment accumulation in the outer retina and attenuation of the retinal vessels. The pathophysiology of RP involves apoptosis of rod cells. Although macular vision is preserved in the initial stages of the disease, visual field defects gradually increase and cone affectation follows. RP can be inherited as an autosomal dominant, autosomal recessive, digenic, or X linked trait. Several RP genes and loci have been described to date (RetNet web site: http://utsph.sph.uth.tmc.edu/www/Wtsph/RetNet/home.htm). Altogether, the genes known to cause the autosomal recessive forms explain a small proportion of cases, while the great majority remain unexplained, which illustrates the extreme genetic heterogeneity of this condition. As expected, many of the ARRP genes are rod specific, some are only expressed in the retinal pigment epithelium, and none is cone specific.

    Cyclic nucleotide gated channels (CNCG) are a group of non-selective ion channels present in different tissues. The rod cGMP gated cation channel is located in the outer segment of the plasma membrane and is involved in the last step of the phototransduction cascade. In spite of a similar function, rod and cone cells express different CNCG genes.1 Rod channels are predicted to form heterotetramers of two alpha and beta subunit dimers. Each contains a core structural unit of six membrane spanning segments, a pore region, and a cGMP binding domain. The alpha peptide (CNGA1, MIM 123825, GDB 127557) forms a functional channel by itself and is considered the main functional subunit, while the beta counterpart (CNGB1, MIM 600724, GDB 434397) modulates the activity of the channel and is unable to promote ion transfer by …