Genetic Mapping and Evaluation of PDE6A in 49 Spanish Families with Autosomal Recessive Retinitis Pigmentosa

  • A. Martínez-Mir
  • E. Paloma
  • S. Balcells
  • L. Vilageliu
  • S. J. Pittler
  • R. Gonzàlez-Duarte


Autosomal recessive retinitis pigmentosa (arRP) is a degenerative disease of photoreceptors in which defects in the genes encoding rhodopsin (RHO), α and β subunits of the cGMP phosphodiesterase (PDE6A and PDE6B, respectively), α subunit of the cGMP gated channel (CNCG), RPE65 and retinaldehyde-binding protein 1 (RLBP1) have been reported. Additionally, linkage analyses have defined four arRP loci on 1q31-q32 (RP12), 6p21.3 (RP14; mutations in the TULP1 gene), 1p13-p21 (RP19; mutation in the ABCR gene), and 2q31–33. However, the molecular basis of the disease has not been ascertained in over 50% of cases, yet.

The PDE6A gene encodes the rod specific form of the a subunit of cGMP phosphodiesterase (PDE6). Together, theα and β subunits of cGMP PDE6 catalyze the breakdown of cGMP in response to light, a critical step in the light transduction pathway. The PDE6B gene has been analyzed in several arRP populations and it appears to account for less than 5% of all arRP cases. In contrast, fewer mutations have been reported in the PDE6A gene in arRP patients. Here we describe the genetic mapping of the PDE6A gene and the analysis of its involvement in arRP in 49 Spanish families. Linkage analysis performed in the CEPH panel of families allowed us to localize the gene at OcM from D5S434 (Z = 10.5). Cosegregation and homozygosity studies with an intragenic polymorphism, a very close marker (D5S434) and two flanking markers (D5S2013 and D5S436) ruled out PDE6A as the cause of arRP in 38 pedigrees. In the eleven remaining families, SSCP analysis of the PD E6A-coding region did not detect any disease causing mutation in the affected members. These results strongly suggest that mutations in the PDE6A gene are not responsible for arRP in these families.


Retinitis Pigmentosa Marker D5S434 SSCP Analysis Spanish Family Degenerative Retinal Disease 
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Copyright information

© Kluwer Academic / Plenum Publishers 1999

Authors and Affiliations

  • A. Martínez-Mir
    • 1
  • E. Paloma
    • 1
  • S. Balcells
    • 1
  • L. Vilageliu
    • 1
  • S. J. Pittler
    • 2
  • R. Gonzàlez-Duarte
    • 1
  1. 1.Departament de Genètica, Facultat de BiologiaUniversität de BarcelonaBarcelonaSpain
  2. 2.Departments of Biochemistry and Molecular Biology, Ophthalmology and the Center for Eye ResearchUniversity of South Alabama College of Medicine MobileAlabama

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