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Naveen Mysore, Ahmed A. Basheikh, Huanan Ren, Jeremy Schwartzentruber, Vafa Kesar, Qing Fu, Ayesha Khan, Irma Lopez-Solache, Jacek Majewski, Robert K. Koenekoop; A New Gene for Crystalline Retinal Dystrophy on the X Chromosome. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4539.
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© ARVO (1962-2015); The Authors (2016-present)
Bietti’s crystalline dystrophy (BCD) is a rare retinal dystrophy with autosomal recessive inheritance. Patients with BCD have CYP4V2 mutations and surprisingly, an abnormal fatty acid profile. The aim of our study is to describe the phenotype and genotype of a new crystalline dystrophy with X-linked inheritance.
A proband (SG: 56 years old), his brother (DD: 53 years old) and mother (SD: 81 years old), who are of Sri Lankan origin, were recruited. Characterization of the phenotypes was done through history, physical exam, Goldmann visual field testing and fundus photography. Heidelberg spectralis OCT and fundus autofluorescence were used to look for retinal crystals and abnormalities in lipofuscin metabolism. Peripheral blood samples were drawn and a fatty acid panel was done on the proband. Electron microscopy (EM) on the blood sample was used to identify crystals in white blood cells. Also, Sanger sequencing of CYP4V2 and next generation sequencing (NGS) was performed. For NGS, we use an Agilent SureSelect 50 Mb kit to identify single nucleotide variants on homologous regions on the X chromosome of SG and DD.
SG and DD describe a 10-year history of worsening night blindness, decreased color vision and tunnel vision. In contrast, the mother did not have night blindness. The visual acuities were 20/30, counting fingers, 20/60 OU for SG, DD, SD, respectively. The anterior segment was unremarkable (SD had prior cataract surgery). The posterior segment showed severe retinal pigment epithelial (RPE) atrophy in SG and DD with macular sparing. SD had mosaic retinal changes. Goldmann visual field testing showed significantly constricted visual fields for SG and DD, while SD had moderate visual field constriction. OCT showed crystals in the subretinal space in SG and DD. Biochemical analysis of the proband revealed fatty acid elevations in C16:0, C18:3n3, C18:2n6, C24:0, C26:0. In contrast, BCD patients have elevations in C18:0, C18:1n9, C20:3n6, C22:5n3, C24:1. Sanger sequencing showed that none of the patients have a CYP4V2 mutation. We are currently analyzing the data from our EM and NGS studies.
This study identified a new X-linked inheritance pattern for a Sri Lankan family with crystalline retinal dystrophy. While the proband and his brother had significant disease burden, the mother showed retinal mosaicism and was not severely affected. The fatty acid profile of the proband is distinct from normal individuals and from Bietti’s patients. EM and NGS studies will be reported. We will show the results of NGS on the X-chromosome of SG and DD. This study shows that crystalline dystrophy can be due to another gene, which is different from BCD. Our next step is to identify other patients, who have X-linked crystalline dystrophy.
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