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Dror Sharon, Dikla Bandah-Rozenfeld, Alexey Obolensky, Liliana Mizrahi-Meissonnier, Tamar Ben-Yosef, Sharon B. Schwartz, Artur V. Cideciyan, Samuel G. Jacobson, Eyal Banin; Mutation Survey of FAM161A in Patients with Retinitis Pigmentosa and Analysis of Protein Localization in the Human Retina. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5388.
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© ARVO (1962-2015); The Authors (2016-present)
We recently reported the identification of FAM161A as a major cause of autosomal recessive retinitis pigmentosa (arRP) due to null mutations in the Israeli population. The current study extends the mutation analysis of FAM161A in the Jewish population and explores localization of the protein in the human retina.
Clinical and molecular analyses included family history, ocular examination, full-field electroretinography (ERG), perimetry, homozygosity mapping and mutation analysis. Immunohistochemistry was performed on retinal sections using antibodies raised against different parts of the protein.
We previously reported that the most common FAM161A mutations in the Jewish population are c.1355_6delCA (p.T452SerfsX3) and c.1567C>T (p.R523X). Genotyping of these mutations in a large cohort of Jewish RP patients from Israel and USA revealed a prevalence of 11% (21/193) and 3% (5/193), respectively, in this population. Due to the high carrier frequency of the c.1355_6delCA mutation in the North African Jewish sub-population (carrier frequency of 1 out of 32 individuals), homozygosity for this mutation was also identified in families with an autosomal pseudo-dominant pattern of inheritance. The majority of patients with FAM161A mutations had an RP phenotype; one patient manifested an atypical retinal degeneration. The FAM161A protein was studied in the human retina by immunohistochemistry, using the HPA032119 antibody. The analysis revealed a positive and intense signal in photoreceptor inner segments as well as weaker staining in the outer plexiform layer. No expression was evident in photoreceptor outer segments. To gain further understanding of FAM161A expression, we raised antibodies against the C-terminal, N-terminal, and the alternatively-spliced and highly conserved exon 4 of FAM161A. The data of protein localization experiments using these antibodies will be presented at the meeting.
FAM161A mutations are currently the most common cause of arRP in the Jewish population (14%). The data we provide here bring to 30 the number of arRP families with FAM161A mutations originating from Europe, India, and Israel.
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