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Mutations of VMD2 splicing regulators cause nanophthalmos and autosomal dominant vitreoretinochoroidopathy (ADVIRC)

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Organization
Abstract
PURPOSE. To investigate the genetic basis of autosomal dominant vitreoretinochoroidopathy (ADVIRC), a rare, inherited retinal dystrophy that may be associated with defects of ocular development, including nanophthalmos. METHODS. A combination of linkage analysis and DNA sequencing in five families was used to identify disease-causing mutations in VMD2. The effect of these mutations on splicing was assessed using a minigene system. RESULTS. Three pathogenic sequence alterations in VMD2 were identified in five families with nanophthalmos associated with ADVIRC. All sequences showed simultaneous missense substitutions and exon skipping. CONCLUSIONS. VMD2 encodes bestrophin, a transmembrane protein located at the basolateral membrane of the RPE, that is also mutated in Best macular dystrophy. We support that each heterozygous affected individual produces three bestrophin isoforms consisting of the wild type and two abnormal forms: one containing a missense substitution and the other an inframe deletion. The data showed that VMD2 mutations caused defects of ocular patterning, supporting the hypothesized role for the RPE, and specifically VMD2, in the normal growth and development of the eye.
Keywords
TRANSCRIPTION FACTOR, MACULAR DYSTROPHY, GENE, FAMILY, IDENTIFICATION, CATARACT, MICROCORNEA, EPITHELIUM, BESTROPHIN, DYSPLASIA

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MLA
Yardley, Jill, Bart Leroy, Niki Hart-Holden, et al. “Mutations of VMD2 Splicing Regulators Cause Nanophthalmos and Autosomal Dominant Vitreoretinochoroidopathy (ADVIRC).” INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE 45.10 (2004): 3683–3689. Print.
APA
Yardley, J., Leroy, B., Hart-Holden, N., Lafaut, B., Loeys, B., Messiaen, L., Perveen, R., et al. (2004). Mutations of VMD2 splicing regulators cause nanophthalmos and autosomal dominant vitreoretinochoroidopathy (ADVIRC). INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 45(10), 3683–3689.
Chicago author-date
Yardley, Jill, Bart Leroy, Niki Hart-Holden, Bart Lafaut, Bart Loeys, Ludwine Messiaen, Rahat Perveen, et al. 2004. “Mutations of VMD2 Splicing Regulators Cause Nanophthalmos and Autosomal Dominant Vitreoretinochoroidopathy (ADVIRC).” Investigative Ophthalmology & Visual Science 45 (10): 3683–3689.
Chicago author-date (all authors)
Yardley, Jill, Bart Leroy, Niki Hart-Holden, Bart Lafaut, Bart Loeys, Ludwine Messiaen, Rahat Perveen, M Ashwin Reddy, Shomi S Bhattacharya, Elias Traboulsi, Diana Baralle, Jean Delaey, Bernard Puech, Philippe Kestelyn, Anthony T Moore, Forbes DC Manson, and Graeme CM Black. 2004. “Mutations of VMD2 Splicing Regulators Cause Nanophthalmos and Autosomal Dominant Vitreoretinochoroidopathy (ADVIRC).” Investigative Ophthalmology & Visual Science 45 (10): 3683–3689.
Vancouver
1.
Yardley J, Leroy B, Hart-Holden N, Lafaut B, Loeys B, Messiaen L, et al. Mutations of VMD2 splicing regulators cause nanophthalmos and autosomal dominant vitreoretinochoroidopathy (ADVIRC). INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE. 2004;45(10):3683–9.
IEEE
[1]
J. Yardley et al., “Mutations of VMD2 splicing regulators cause nanophthalmos and autosomal dominant vitreoretinochoroidopathy (ADVIRC),” INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, vol. 45, no. 10, pp. 3683–3689, 2004.
@article{316696,
  abstract     = {{PURPOSE. To investigate the genetic basis of autosomal dominant vitreoretinochoroidopathy (ADVIRC), a rare, inherited retinal dystrophy that may be associated with defects of ocular development, including nanophthalmos. 
METHODS. A combination of linkage analysis and DNA sequencing in five families was used to identify disease-causing mutations in VMD2. The effect of these mutations on splicing was assessed using a minigene system. 
RESULTS. Three pathogenic sequence alterations in VMD2 were identified in five families with nanophthalmos associated with ADVIRC. All sequences showed simultaneous missense substitutions and exon skipping. 
CONCLUSIONS. VMD2 encodes bestrophin, a transmembrane protein located at the basolateral membrane of the RPE, that is also mutated in Best macular dystrophy. We support that each heterozygous affected individual produces three bestrophin isoforms consisting of the wild type and two abnormal forms: one containing a missense substitution and the other an inframe deletion. The data showed that VMD2 mutations caused defects of ocular patterning, supporting the hypothesized role for the RPE, and specifically VMD2, in the normal growth and development of the eye.}},
  author       = {{Yardley, Jill and Leroy, Bart and Hart-Holden, Niki and Lafaut, Bart and Loeys, Bart and Messiaen, Ludwine and Perveen, Rahat and Reddy, M Ashwin and Bhattacharya, Shomi S and Traboulsi, Elias and Baralle, Diana and Delaey, Jean and Puech, Bernard and Kestelyn, Philippe and Moore, Anthony T and Manson, Forbes DC and Black, Graeme CM}},
  issn         = {{0146-0404}},
  journal      = {{INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE}},
  keywords     = {{TRANSCRIPTION FACTOR,MACULAR DYSTROPHY,GENE,FAMILY,IDENTIFICATION,CATARACT,MICROCORNEA,EPITHELIUM,BESTROPHIN,DYSPLASIA}},
  language     = {{eng}},
  number       = {{10}},
  pages        = {{3683--3689}},
  title        = {{Mutations of VMD2 splicing regulators cause nanophthalmos and autosomal dominant vitreoretinochoroidopathy (ADVIRC)}},
  url          = {{http://dx.doi.org/10.1167/iovs.04-0550}},
  volume       = {{45}},
  year         = {{2004}},
}

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