Showing papers by "Bart P. Leroy published in 2004"

Mutations of VMD2 Splicing Regulators Cause Nanophthalmos and Autosomal Dominant Vitreoretinochoroidopathy (ADVIRC)

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.

Clinical features & retinal function in patients with adult Refsum syndrome.

Abstract: Purpose: To characterise the clinical findings, and retinal function in patients with Adult Refsum Syndrome (ARS) using clinical examination and electroretinography, and to evaluate possible effects of treatment. ARS is an autosomal recessive peroxisomal multisystem disorder with accumulation of phytanic acid (PhyAc) (Jansen et al, 1997). Mutations have been identified in the gene encoding human phytanoyl-CoA a-hydroxylase (Jansen et al, 1997, Mihalik et al, 1997) and recently in PEX7 (van den Brink et al, 2003). The classical clinical features of the condition are retinitis pigmentosa, peripheral polyneuropathy, cerebellar ataxia and high protein levels in CSF in the absence of hypercellularity (Wanders et al, 2001). The disease is treatable by a PhyAc restriction diet, either alone, or in combination with plasmapheresis (Wanders et al, 2001). Only a limited amount of patients have been studied with visual electrophysiology to date (Berson, 1987 and Claridge et al, 1992).