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J Med Genet 37:e5 doi:10.1136/jmg.37.6.e5
  • Electronic letters

Mutation analysis of GABRR1 andGABRR2 in autosomal recessive retinitis pigmentosa (RP25)

  1. I MARCOS*,
  2. A RUIZ*,
  3. C J BLASCHAK,
  4. S BORREGO*,
  5. G R CUTTING,
  6. G ANTIÑOLO*
  1. * Unidad de Genética Médica y Diagnóstico Prenatal, Hospital Universitario “Virgen del Rocío”, Avenida Manuel Siurot s/n, 41013 Sevilla, Spain
  2. Center for Medical Genetics, Johns Hopkins Hospital, Baltimore, Maryland, USA
  1. Dr Antiñolo, gantinolog{at}sego.es

    Editor—Retinitis pigmentosa (RP, MIM 268000) is the most frequent form of retinal dystrophy world wide. The clinical findings are night blindness and narrowing of the visual field. Examination of the fundus of the eye in RP patients usually shows bone spicula pigmentation of the retina, waxy pallor of the optic disc, attenuation of the retinal blood vessels, and no results detectable by electroretinogram.1

    RP shows notable allelic and non-allelic heterogeneity2(RET-GEN-NET htp://www.sph.uth.tm.edu/Retnet/home.htm). By using classical linkage strategies and the direct and indirect candidate gene approach, the number of RP loci identified has grown increasingly since 1989 and to date more than 30 autosomal RP loci have been identified, including syndromic and non-syndromic forms of the disease. Autosomal recessive RP (ARRP) is the commonest form of RP and to date at least 13 independent ARRP loci have been identified.3-15

    Our group proposed the hypothesis that the alteration of functions related to neurotransmission in the external plexiform layer of the retina could be related to RP.14 In order to test this model, we used homozygosity mapping to analyse different genes involved in retinal neurotransmission. Using this indirect candidate gene approach, we identified the locus RP25 in an important subgroup of ARRP patients from our cohort. In fact, around 14% of the ARRP families from southern Spain showed linkage toRP25. 14 RP25 is an ARRP locus located on the long arm of chromosome 6 between markers D6S257 and D6S1644 (MIM 602772). This chromosomal region contains the GABRR1and GABRR2 genes, both being expressed in the retina. These genes encode the rho1 and rho2 subunits of the C type receptor for γ-aminobutyric acid (GABAc receptor).16 17The GABAc …