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Mutations in IFT172 cause isolated retinal degeneration and Bardet-Biedl syndrome

(2015) HUMAN MOLECULAR GENETICS. 24(1). p.230-242
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Abstract
Primary cilia are sensory organelles present on most mammalian cells. The assembly and maintenance of primary cilia are facilitated by intraflagellar transport (IFT), a bidirectional protein trafficking along the cilium. Mutations in genes coding for IFT components have been associated with a group of diseases called ciliopathies. These genetic disorders can affect a variety of organs including the retina. Using whole exome sequencing in three families we identified mutations in IFT172 [Intraflagellar Transport 172 Homolog (Chlamydomonas)] that underlie an isolated retinal degeneration and Bardet-Biedl syndrome. Extensive functional analyses of the identified mutations in cell culture, rat retina and in zebrafish demonstrated their hypomorphic or null nature. It has recently been reported that mutations in IFT172 cause a severe ciliopathy syndrome involving skeletal, renal, hepatic and retinal abnormalities (Jeune and Mainzer-Saldino syndromes). Here, we report for the first time that mutations in this gene can also lead to an isolated form of retinal degeneration. The functional data for the mutations can partially explain milder phenotypes; however the involvement of modifying alleles in the IFT172-associated phenotypes cannot be excluded. These findings expand the spectrum of disease associated with mutations in IFT172, and suggest that mutations in genes originally reported to be associated with syndromic ciliopathies should also be considered in subjects with non-syndromic retinal dystrophy.
Keywords
NONSYNDROMIC RETINITIS-PIGMENTOSA, GENE ABCR, JOUBERT-SYNDROME, STATIONARY NIGHT BLINDNESS, LEBER CONGENITAL AMAUROSIS, INTRAFLAGELLAR TRANSPORT PROTEIN, CENTROSOMAL PROTEIN, DYSTROPHY, CILIARY, IN-VIVO

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Chicago
Bujakowska, Kinga M, Qi Zhang, Anna M Siemiatkowska, Qin Liu, Emily Place, Marni J Falk, Mark Consugar, et al. 2015. “Mutations in IFT172 Cause Isolated Retinal Degeneration and Bardet-Biedl Syndrome.” Human Molecular Genetics 24 (1): 230–242.
APA
Bujakowska, K. M., Zhang, Q., Siemiatkowska, A. M., Liu, Q., Place, E., Falk, M. J., Consugar, M., et al. (2015). Mutations in IFT172 cause isolated retinal degeneration and Bardet-Biedl syndrome. HUMAN MOLECULAR GENETICS, 24(1), 230–242.
Vancouver
1.
Bujakowska KM, Zhang Q, Siemiatkowska AM, Liu Q, Place E, Falk MJ, et al. Mutations in IFT172 cause isolated retinal degeneration and Bardet-Biedl syndrome. HUMAN MOLECULAR GENETICS. 2015;24(1):230–42.
MLA
Bujakowska, Kinga M, Qi Zhang, Anna M Siemiatkowska, et al. “Mutations in IFT172 Cause Isolated Retinal Degeneration and Bardet-Biedl Syndrome.” HUMAN MOLECULAR GENETICS 24.1 (2015): 230–242. Print.
@article{5695910,
  abstract     = {Primary cilia are sensory organelles present on most mammalian cells. The assembly and maintenance of primary cilia are facilitated by intraflagellar transport (IFT), a bidirectional protein trafficking along the cilium. Mutations in genes coding for IFT components have been associated with a group of diseases called ciliopathies. These genetic disorders can affect a variety of organs including the retina. Using whole exome sequencing in three families we identified mutations in IFT172 [Intraflagellar Transport 172 Homolog (Chlamydomonas)] that underlie an isolated retinal degeneration and Bardet-Biedl syndrome. Extensive functional analyses of the identified mutations in cell culture, rat retina and in zebrafish demonstrated their hypomorphic or null nature. It has recently been reported that mutations in IFT172 cause a severe ciliopathy syndrome involving skeletal, renal, hepatic and retinal abnormalities (Jeune and Mainzer-Saldino syndromes). Here, we report for the first time that mutations in this gene can also lead to an isolated form of retinal degeneration. The functional data for the mutations can partially explain milder phenotypes; however the involvement of modifying alleles in the IFT172-associated phenotypes cannot be excluded. These findings expand the spectrum of disease associated with mutations in IFT172, and suggest that mutations in genes originally reported to be associated with syndromic ciliopathies should also be considered in subjects with non-syndromic retinal dystrophy.},
  author       = {Bujakowska, Kinga M and Zhang, Qi and Siemiatkowska, Anna M and Liu, Qin and Place, Emily and Falk, Marni J and Consugar, Mark and Lancelot, Marie-Elise and Antonio, Aline and Lonjou, Christine and Carpentier, Wassila and Mohand-Saїd, Saddek and den Hollander, Anneke I and Cremers, Frans PM and Leroy, Bart and Gai, Xiaowu and Sahel, José-Alain and van den Born, L Ingeborgh and Collin, Rob WJ and Zeitz, Christina and Audo, Isabelle and Pierce, Eric A},
  issn         = {0964-6906},
  journal      = {HUMAN MOLECULAR GENETICS},
  keywords     = {NONSYNDROMIC RETINITIS-PIGMENTOSA,GENE ABCR,JOUBERT-SYNDROME,STATIONARY NIGHT BLINDNESS,LEBER CONGENITAL AMAUROSIS,INTRAFLAGELLAR TRANSPORT PROTEIN,CENTROSOMAL PROTEIN,DYSTROPHY,CILIARY,IN-VIVO},
  language     = {eng},
  number       = {1},
  pages        = {230--242},
  title        = {Mutations in IFT172 cause isolated retinal degeneration and Bardet-Biedl syndrome},
  url          = {http://dx.doi.org/10.1093/hmg/ddu441},
  volume       = {24},
  year         = {2015},
}

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