June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Comprehensive molecular diagnosis of a large cohort of 240 autosomal dominant retinitis pigmentosa families by Sanger and targeted next generation sequencing
Author Affiliations & Notes
  • Gael Manes
    INSERM U1051, Institute for Neurosciences of Montepllier, Montpellier, France
    University of Montpellier 2, Montpellier, France
  • Tremeur Guillaumie
    Genetics of Sensory Diseases, Centre hospitalier régional universitaire, Montpellier, France
  • Isabelle S Audo
    INSERM U968, Paris, France
    Institut de la Vision, Sorbonne Universités, UPMC Univ Paris 06, Paris, France
  • Christina Zeitz
    INSERM U968, Paris, France
    Institut de la Vision, Sorbonne Universités, UPMC Univ Paris 06, Paris, France
  • Aurore Devos
    Laboratoire de Biochimie et Biologie Moléculaire, CHRU Lille, Lille, France
  • Béatrice Bocquet
    INSERM U1051, Institute for Neurosciences of Montepllier, Montpellier, France
    Genetics of Sensory Diseases, Centre hospitalier régional universitaire, Montpellier, France
  • Corinne Baudoin
    INSERM U1051, Institute for Neurosciences of Montepllier, Montpellier, France
    Genetics of Sensory Diseases, Centre hospitalier régional universitaire, Montpellier, France
  • Isabelle Meunier
    INSERM U1051, Institute for Neurosciences of Montepllier, Montpellier, France
    Genetics of Sensory Diseases, Centre hospitalier régional universitaire, Montpellier, France
  • Claire-Marie Dhaenens
    Laboratoire de Biochimie et Biologie Moléculaire, CHRU Lille, Lille, France
    Université Lille Nord de France, Lille, France
  • Christian P Hamel
    INSERM U1051, Institute for Neurosciences of Montepllier, Montpellier, France
    Genetics of Sensory Diseases, Centre hospitalier régional universitaire, Montpellier, France
  • Footnotes
    Commercial Relationships Gael Manes, None; Tremeur Guillaumie, None; Isabelle Audo, None; Christina Zeitz, None; Aurore Devos, None; Béatrice Bocquet, None; Corinne Baudoin, None; Isabelle Meunier, None; Claire-Marie Dhaenens, None; Christian Hamel, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 1264. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Gael Manes, Tremeur Guillaumie, Isabelle S Audo, Christina Zeitz, Aurore Devos, Béatrice Bocquet, Corinne Baudoin, Isabelle Meunier, Claire-Marie Dhaenens, Christian P Hamel, ; Comprehensive molecular diagnosis of a large cohort of 240 autosomal dominant retinitis pigmentosa families by Sanger and targeted next generation sequencing. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1264.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose: To screen a cohort of 240 families with ascertained autosomal dominant retinitis pigmentosa (adRP) condition for mutations in genes known to cause adRP.

Methods: Two hundred and forty well-characterized adRP families were recruited mostly originating from France. The ten most frequently mutated adRP genes (RHO and PRPH2 in all exons, PRPF31, RP1, PRPF8, IMPDH1, NRL, PRPF3, NR2E3 and SNRNP200 in hot spots regions) were screened for mutations by Sanger sequencing of the probands. Patients without identified mutations were then sequenced using a targeted exon capture panel, which includes 123 retinal disease genes containing the 69 known adRP, autosomal recessive (arRP) and X-linked RP genes and several other retinal dystrophy genes.

Results: Disease-causing mutations were identified in 152 probands (62.5%), among which 43% had novel mutations. Four major genes, RHO (17.5%), PRPH2 (10.5%), RP1 (7.1%) and PRPF31 (6.3%) accounted for 41.5% of the cohort. Some genes revealed unexpectedly high prevalence of mutations: NR2E3 (4.6%), SNRNP200 (3.3%) and TOPORS (2.1%). No mutations were identified in nine adRP (CA4, FSCN2, GUCA1B, NRL, PRPF6, RDH12, ROM1, RP9/PAP1 and SEMA4A) and in arRP genes. Phenotype analysis showed moderate RP in many patients, with remarkable incomplete penetrance in PRPF31, SNRNP200 and RP1, and highly variable phenotype in PRPH2 including pericentral RP, diffuse RP and pseudovitelliform macular dystrophy in RP families.

Conclusions: Almost 2/3 of the families (62.5%) carry a mutation in a known adRP gene, implying that more than 1/3 (37.5%) of the families either have deep intronic mutations in a known gene, large chromosomal rearrangement not detected by techniques applied or are mutated in an unknown RP gene. Full exome sequencing is currently ongoing for 21 negative families.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×