1. Mutations in IMPG1 Cause Vitelliform Macular Dystrophies
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Hélène Dollfus, Susanne Kohl, Maxime Hebrard, Philippe Brabet, Isabelle Meunier, Audrey Sénéchal, Elfride De Baere, Carmen Ayuso García, Christina Zeitz, Béatrice Bocquet, Sandro Banfi, Guylène Le Meur, Claire Marie Dhaenens, Delphine Allorge, Frans P.M. Cremers, Francesca Simonelli, Michel Weber, Joe G. Hollyfield, Saddek Mohand-Said, Christian P. Hamel, Gaël Manes, Marta Corton, Xavier Zanlonghi, Robert K. Koenekoop, Gilles Labesse, Almudena Avila-Fernandez, José-Alain Sahel, Isabelle Audo, Manes, G, Meunier, I, Avila Fernández, A, Banfi, Sandro, Le Meur, G, Zanlonghi, X, Corton, M, Simonelli, Francesca, Brabet, P, Labesse, G, Audo, I, Mohand Said, S, Zeitz, C, Sahel, Ja, Weber, M, Dollfus, H, Dhaenens, Cm, Allorge, D, De Baere, E, Koenekoop, Rk, Kohl, S, Cremers, Fp, Hollyfield, Jg, Sénéchal, A, Hebrard, M, Bocquet, B, Ayuso García, C, and Hamel, Cp
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Adult ,Male ,Proband ,Genetics and epigenetic pathways of disease [NCMLS 6] ,genetic structures ,Fundus Oculi ,Molecular Sequence Data ,Inheritance Patterns ,Vitelliform macular dystrophy ,Biology ,Interphotoreceptor matrix ,medicine.disease_cause ,Compound heterozygosity ,Young Adult ,Report ,medicine ,Genetics ,Chromosomes, Human ,Humans ,Genetic Predisposition to Disease ,Genetics(clinical) ,Amino Acid Sequence ,Eye Proteins ,Genetics (clinical) ,Extracellular Matrix Proteins ,Mutation ,Base Sequence ,Genetic heterogeneity ,Middle Aged ,Macular dystrophy ,medicine.disease ,eye diseases ,Pedigree ,Vitelliform Macular Dystrophy ,Phenotype ,Female ,Proteoglycans ,sense organs ,Retinal Dystrophies - Abstract
Item does not contain fulltext 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.Arg507( *)). 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.
- Published
- 2013
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