Molecular genetics of FAM161A in North American patients with early-onset retinitis pigmentosa.

Retinitis pigmentosa (RP) is a hereditary disease that leads to the progressive degeneration of retinal photoreceptor cells and to blindness. It is caused by mutations in several distinct genes, including the ciliary gene FAM161A, which is associated with a recessive form of this disorder. Recent in...

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Autores principales:	Giulia Venturini, Silvio Alessandro Di Gioia, Shyana Harper, Carol Weigel-DiFranco, Carlo Rivolta, Eliot L Berson
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e7a79b73135947b3ae4576d6a5f86c19
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spelling	oai:doaj.org-article:e7a79b73135947b3ae4576d6a5f86c192021-11-18T08:27:05ZMolecular genetics of FAM161A in North American patients with early-onset retinitis pigmentosa.1932-620310.1371/journal.pone.0092479https://doaj.org/article/e7a79b73135947b3ae4576d6a5f86c192014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24651477/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Retinitis pigmentosa (RP) is a hereditary disease that leads to the progressive degeneration of retinal photoreceptor cells and to blindness. It is caused by mutations in several distinct genes, including the ciliary gene FAM161A, which is associated with a recessive form of this disorder. Recent investigations have revealed that defects in FAM161A represent a rather prevalent cause of hereditary blindness in Israel and the Palestinian territories, whereas they seem to be rarely present within patients from Germany. Genetic or clinical data are currently not available for other countries. In this work, we screened a cohort of patients with recessive RP from North America to determine the frequency of FAM161A mutations in this ethnically-mixed population and to assess the phenotype of positive cases. Out of 273 unrelated patients, only 3 subjects had defects in FAM161A. A fourth positive patient, the sister of one of these index cases, was also identified following pedigree analysis. They were all homozygous for the p.T452Sfx3 mutation, which was previously reported as a founder DNA variant in the Israeli and Palestinian populations. Analysis of cultured lymphoblasts from patients revealed that mutant FAM161A transcripts were actively degraded by nonsense-mediated mRNA decay. Electroretinographic testing showed 30 Hz cone flicker responses in the range of 0.10 to 0.60 microvolts in all cases at their first visit (age 12 to 23) (lower norm = 50 μV) and of 0.06 to 0.32 microvolts at their most recent examination (age 27 to 43), revealing an early-onset of this progressive disease. Our data indicate that mutations in FAM161A are responsible for 1% of recessive RP cases in North America, similar to the prevalence detected in Germany and unlike the data from Israel and the Palestinian territories. We also show that, at the molecular level, the disease is likely caused by FAM161A protein deficiency.Giulia VenturiniSilvio Alessandro Di GioiaShyana HarperCarol Weigel-DiFrancoCarlo RivoltaEliot L BersonPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 3, p e92479 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Giulia Venturini Silvio Alessandro Di Gioia Shyana Harper Carol Weigel-DiFranco Carlo Rivolta Eliot L Berson Molecular genetics of FAM161A in North American patients with early-onset retinitis pigmentosa.
description	Retinitis pigmentosa (RP) is a hereditary disease that leads to the progressive degeneration of retinal photoreceptor cells and to blindness. It is caused by mutations in several distinct genes, including the ciliary gene FAM161A, which is associated with a recessive form of this disorder. Recent investigations have revealed that defects in FAM161A represent a rather prevalent cause of hereditary blindness in Israel and the Palestinian territories, whereas they seem to be rarely present within patients from Germany. Genetic or clinical data are currently not available for other countries. In this work, we screened a cohort of patients with recessive RP from North America to determine the frequency of FAM161A mutations in this ethnically-mixed population and to assess the phenotype of positive cases. Out of 273 unrelated patients, only 3 subjects had defects in FAM161A. A fourth positive patient, the sister of one of these index cases, was also identified following pedigree analysis. They were all homozygous for the p.T452Sfx3 mutation, which was previously reported as a founder DNA variant in the Israeli and Palestinian populations. Analysis of cultured lymphoblasts from patients revealed that mutant FAM161A transcripts were actively degraded by nonsense-mediated mRNA decay. Electroretinographic testing showed 30 Hz cone flicker responses in the range of 0.10 to 0.60 microvolts in all cases at their first visit (age 12 to 23) (lower norm = 50 μV) and of 0.06 to 0.32 microvolts at their most recent examination (age 27 to 43), revealing an early-onset of this progressive disease. Our data indicate that mutations in FAM161A are responsible for 1% of recessive RP cases in North America, similar to the prevalence detected in Germany and unlike the data from Israel and the Palestinian territories. We also show that, at the molecular level, the disease is likely caused by FAM161A protein deficiency.
format	article
author	Giulia Venturini Silvio Alessandro Di Gioia Shyana Harper Carol Weigel-DiFranco Carlo Rivolta Eliot L Berson
author_facet	Giulia Venturini Silvio Alessandro Di Gioia Shyana Harper Carol Weigel-DiFranco Carlo Rivolta Eliot L Berson
author_sort	Giulia Venturini
title	Molecular genetics of FAM161A in North American patients with early-onset retinitis pigmentosa.
title_short	Molecular genetics of FAM161A in North American patients with early-onset retinitis pigmentosa.
title_full	Molecular genetics of FAM161A in North American patients with early-onset retinitis pigmentosa.
title_fullStr	Molecular genetics of FAM161A in North American patients with early-onset retinitis pigmentosa.
title_full_unstemmed	Molecular genetics of FAM161A in North American patients with early-onset retinitis pigmentosa.
title_sort	molecular genetics of fam161a in north american patients with early-onset retinitis pigmentosa.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/e7a79b73135947b3ae4576d6a5f86c19
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Molecular genetics of FAM161A in North American patients with early-onset retinitis pigmentosa.

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