September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Investigating the pathomechanism of FAM161A-associated retinal disease in primary ciliated cells
Author Affiliations & Notes
  • Heidi Barbara Stoehr
    Human Genetics, University Regensburg, Regensburg, Germany
  • Marlene Schwarzfischer
    Human Genetics, University Regensburg, Regensburg, Germany
  • Lisa-Marie Braun
    Human Genetics, University Regensburg, Regensburg, Germany
  • Alexander Aslanidis
    Laboratory for Experimental Immunology of the Eye, University Cologne, Cologne, Germany
  • Thomas Langmann
    Laboratory for Experimental Immunology of the Eye, University Cologne, Cologne, Germany
  • Ulrich Kellner
    MVZ ADTC Siegburg GmbH, Rare Retinal Disease Center, Siegburg, Germany
    RetinaScience, Bonn, Germany
  • Footnotes
    Commercial Relationships   Heidi Stoehr, None; Marlene Schwarzfischer, None; Lisa-Marie Braun, None; Alexander Aslanidis, None; Thomas Langmann, None; Ulrich Kellner, None
  • Footnotes
    Support  DFG Grants STO366/4-1 and LA1203/8-1
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 3192. doi:
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    • Get Citation

      Heidi Barbara Stoehr, Marlene Schwarzfischer, Lisa-Marie Braun, Alexander Aslanidis, Thomas Langmann, Ulrich Kellner; Investigating the pathomechanism of FAM161A-associated retinal disease in primary ciliated cells
      . Invest. Ophthalmol. Vis. Sci. 2016;57(12):3192.

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

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Abstract

Purpose : Loss-of-function mutations in the FAM161A gene cause autosomal recessive retinitis pigmentosa (RP28). We sought to obtain primary ciliated cells lacking FAM161A as a model system to study the pathomechanism underlying FAM161A-associated ciliopathies.

Methods : DNA testing was performed via targeted gene panel diagnostics in a patient with simplex retinitis pigmentosa. Clinical assessment included visual acuity, visual fields, fundus (FAF) and near-infrared autofluorescence (NIA) and spectral domain optical coherence tomography (SD-OCT). RT-PCR was used for mRNA expression analysis. Human dermal fibroblasts and mouse lung fibroblasts were immunostained with antibodies against FAM161A, FAM161B and markers specific for microtubules and the Golgi apparatus.

Results : A 31-year old female from Spain was found to carry a novel homozygous c.730delA;p.Met244* stop mutation in exon 3 of the FAM161A gene. Clinical examination revealed a visual acuity of 20/100 on both eyes, markedly constricted visual fields, FAF and NIA findings characteristic for retinitis pigmentosa. The SD-OCT showed preserved photoreceptor layers at the posterior pole without macular edema. RT-PCR analysis revealed endogenous mRNA expression of FAM161A and FAM161B, a direct interaction partner of FAM161A, in control fibroblast cultures. FAM161A co-localized with acetylated α-tubulin in primary cilia and FAM161B overlapped with γ-tubulin in the basal body. Neither FAM161A nor FAM161B showed overlapping localization with the Golgi marker GM-130.

Conclusions : FAM161A is present in primary cilia of fibroblast cultures. Therefore, fibroblasts or other ciliated cells such as urine-derived renal epithelial cells cultivated from patients or a Fam161a-deficient mouse model can be used for further ex vivo analysis of molecular mechanisms underlying FAM161A-associated disease.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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