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Abstract
Vitelliform macular dystrophies (VMD) are inherited retinal dystrophies characterized by yellow, round deposits visible upon fundus examination and encountered in individuals with juvenile Best macular dystrophy (BMD) or adult-onset vitelliform macular dystrophy (AVMD). Although many BMD and some AVMD cases harbor mutations in BEST1 or PRPH2, the underlying genetic cause remains unknown for many affected individuals. In a large family with autosomal-dominant VMD, gene mapping and whole-exome sequencing led to the identification of a c.713T>G (p.Leu238Arg) IMPG1 mutation, which was subsequently found in two other families with autosomal-dominant VMD and the same phenotype. IMPG1 encodes the SPACR protein, a component of the rod and cone photoreceptor extracellular matrix domains. Structural modeling indicates that the p.Leu238Arg substitution destabilizes the conserved SEA1 domain of SPACR. Screening of 144 probands who had various forms of macular dystrophy revealed three other IMPG1 mutations. Two individuals from one family affected by autosomal-recessive VMD were homozygous for the splice-site mutation c.807+1G>T, and two from another family were compound heterozygous for the mutations c.461T>C (p.Leu154Pro) and c.1519C>T (p.A1g507*). Most cases had a normal or moderately decreased electrooculogram Arden ratio. We conclude that IMPG1 mutations cause both autosomal-dominant and -recessive forms of VMD, thus indicating that impairment of the interphotoreceptor matrix might be a general cause of VMD.
Keywords
INTERPHOTORECEPTOR MATRIX, SEA DOMAIN, BULLS-EYE MACULOPATHY, RECESSIVE RETINITIS-PIGMENTOSA, DISEASE, PROTEOGLYCAN, PHOTORECEPTORS, GENETIC-HETEROGENEITY, VMD2 GENE

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Citation

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Chicago
Manes, Gaël, Isabelle Meunier, Almudena Avila-Fernández, Sandro Banfi, Guylène Le Meur, Xavier Zanlonghi, Marta Corton, et al. 2013. “Mutations in IMPG1 Cause Vitelliform Macular Dystrophies.” American Journal of Human Genetics 93 (3): 571–578.
APA
Manes, G., Meunier, I., Avila-Fernández, A., Banfi, S., Le Meur, G., Zanlonghi, X., Corton, M., et al. (2013). Mutations in IMPG1 cause vitelliform macular dystrophies. AMERICAN JOURNAL OF HUMAN GENETICS, 93(3), 571–578.
Vancouver
1.
Manes G, Meunier I, Avila-Fernández A, Banfi S, Le Meur G, Zanlonghi X, et al. Mutations in IMPG1 cause vitelliform macular dystrophies. AMERICAN JOURNAL OF HUMAN GENETICS. 2013;93(3):571–8.
MLA
Manes, Gaël, Isabelle Meunier, Almudena Avila-Fernández, et al. “Mutations in IMPG1 Cause Vitelliform Macular Dystrophies.” AMERICAN JOURNAL OF HUMAN GENETICS 93.3 (2013): 571–578. Print.
@article{4353905,
  abstract     = {Vitelliform macular dystrophies (VMD) are inherited retinal dystrophies characterized by yellow, round deposits visible upon fundus examination and encountered in individuals with juvenile Best macular dystrophy (BMD) or adult-onset vitelliform macular dystrophy (AVMD). Although many BMD and some AVMD cases harbor mutations in BEST1 or PRPH2, the underlying genetic cause remains unknown for many affected individuals. In a large family with autosomal-dominant VMD, gene mapping and whole-exome sequencing led to the identification of a c.713T{\textrangle}G (p.Leu238Arg) IMPG1 mutation, which was subsequently found in two other families with autosomal-dominant VMD and the same phenotype. IMPG1 encodes the SPACR protein, a component of the rod and cone photoreceptor extracellular matrix domains. Structural modeling indicates that the p.Leu238Arg substitution destabilizes the conserved SEA1 domain of SPACR. Screening of 144 probands who had various forms of macular dystrophy revealed three other IMPG1 mutations. Two individuals from one family affected by autosomal-recessive VMD were homozygous for the splice-site mutation c.807+1G{\textrangle}T, and two from another family were compound heterozygous for the mutations c.461T{\textrangle}C (p.Leu154Pro) and c.1519C{\textrangle}T (p.A1g507*). Most cases had a normal or moderately decreased electrooculogram Arden ratio. We conclude that IMPG1 mutations cause both autosomal-dominant and -recessive forms of VMD, thus indicating that impairment of the interphotoreceptor matrix might be a general cause of VMD.},
  author       = {Manes, Ga{\"e}l and Meunier, Isabelle and Avila-Fern{\'a}ndez, Almudena and Banfi, Sandro and Le Meur, Guyl{\`e}ne and Zanlonghi, Xavier and Corton, Marta and Simonelli, Francesca and Brabet, Philippe and Labesse, Gilles and Audo, Isabelle and Mohand-Said, Saddek and Zeitz, Christina and Sahel, Jos{\'e}-Alain and Weber, Michel and Dollfus, H{\'e}l{\`e}ne and Dhaenens, Claire-Marie and Allorge, Delphine and De Baere, Elfride and Koenekoop, Robert K and Kohl, Susanne and Cremers, Frans PM and Hollyfield, Joe G and Senechal, Audrey and Hebrard, Maxime and Bocquet, Beatrice and Ayuso Garc{\'i}a, Carmen and Hamel, Christian P},
  issn         = {0002-9297},
  journal      = {AMERICAN JOURNAL OF HUMAN GENETICS},
  language     = {eng},
  number       = {3},
  pages        = {571--578},
  title        = {Mutations in IMPG1 cause vitelliform macular dystrophies},
  url          = {http://dx.doi.org/10.1016/j.ajhg.2013.07.018},
  volume       = {93},
  year         = {2013},
}

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