May 2006
Volume 47, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2006
Identification of a Large Insertion/Deletion in the PRPF31 Gene in a Family with adRP
Author Affiliations & Notes
  • L.S. Sullivan
    Univ. of Texas Health Science Center at Houston, Houston, TX
    Human Genetics Center,
  • S.J. Bowne
    Univ. of Texas Health Science Center at Houston, Houston, TX
    Human Genetics Center,
  • C.R. Seaman
    Univ. of Texas Health Science Center at Houston, Houston, TX
    Human Genetics Center,
  • D.G. Birch
    Retina Foundation of the Southwest, Dallas, TX
  • D.H. Wheaton
    Retina Foundation of the Southwest, Dallas, TX
  • R.A. Lewis
    Dept. of Ophthalmology, Baylor College of Medicine, Houston, TX
  • S.H. Blanton
    Dept. of Pediatrics, Univ. of Virginia, Charlottesville, VA
  • S.P. Daiger
    Univ. of Texas Health Science Center at Houston, Houston, TX
    Human Genetics Center and Dept. of Ophthalmology and Visual Sci.,
  • Footnotes
    Commercial Relationships  L.S. Sullivan, None; S.J. Bowne, None; C.R. Seaman, None; D.G. Birch, None; D.H. Wheaton, None; R.A. Lewis, None; S.H. Blanton, None; S.P. Daiger, None.
  • Footnotes
    Support  NIH grants EY07142 and EY05325; the Foundation Fighting Blindness, The William Stamps Farish Fund, The Hermann Eye Fund and Research to Prevent Blindness.
Investigative Ophthalmology & Visual Science May 2006, Vol.47, 1704. doi:
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      L.S. Sullivan, S.J. Bowne, C.R. Seaman, D.G. Birch, D.H. Wheaton, R.A. Lewis, S.H. Blanton, S.P. Daiger; Identification of a Large Insertion/Deletion in the PRPF31 Gene in a Family with adRP . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1704.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : To identify the cause of disease in a large 5–generation family with autosomal dominant retinitis pigmentosa. The presence of several non–penetrant individuals suggested the PRPF31 gene as a likely candidate but X–linked transmission was also considered, given the pedigree structure.

Methods: : Each of the known adRP genes (CA4, FSCN2, IMPDH1, NRL, PRPF3, PRPF8, PRPF31, RDS, RHO, ROM1, RP1, RP9) was screened by DNA sequencing. Linkage testing with polymorphic STR markers at each adRP locus and markers for XlRP loci was performed and LOD scores calculated. SNPs in and around the PRPF31 gene were amplified and sequenced. MLPA (multiplex ligation–dependent probe amplification) and additional family testing confirmed positive results.

Results: : No disease–causing mutations were identified by DNA sequencing of the 12 adRP genes. All adRP and XlRP loci were excluded by linkage testing except PRPF31 which yielded LOD scores >3.0. Sequencing of numerous SNPs in the PRPF31 region in several family members produced inconsistent results, suggesting that some part of the PRPF31 gene was deleted.

Conclusions: : A complex mutation consisting of the deletion of 149 bp at the exon 1/intron 1 junction and the insertion of 640 bp of genomic DNA at the same site appears to be the cause of disease in this family. The mutation is found in all affected family members tested, as well as in obligate carriers who show no sign of disease. The mutation is likely to prevent the splicing of non–coding exon 1 to exon 2, resulting in a null allele.

Keywords: retinal degenerations: hereditary • gene screening • mutations 
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