Novel insights into the molecular pathogenesis of CYP4V2‐associated Bietti's retinal dystrophy. Issue 1 (15th September 2014)

• Record Type: Journal Article
• Authors: Astuti, Galuh D. N.; Sun, Vincent; Bauwens, Miriam; Zobor, Ditta; Leroy, Bart P.; Omar, Amer; Jurklies, Bernhard; Lopez, Irma; Ren, Huanan; Yazar, Volkan; Hamel, Christian; Kellner, Ulrich; Wissinger, Bernd; Kohl, Susanne; De Baere, Elfride; Collin, Rob W. J.; Koenekoop, Robert K.
• Is Part Of: Molecular genetics & genomic medicine. Volume 3:Issue 1(2015:Jan.)
• Page Start: 14
• Page End: 29
• Publication Date: 2014-09-15
• Subjects: Medical genetics -- Periodicals; Genomics -- Periodicals; 616.042
• DOI: 10.1002/mgg3.109
• Languages: English
• ISSNs: 2324-9269

Abstract

<abstract abstract-type="main" id="mgg3109-abs-0001"> <title>Abstract</title> <p>Bietti's crystalline dystrophy (BCD) is a rare, autosomal recessive retinal degenerative disease associated with mutations in <italic>CYP4V2</italic>. In this study, we describe the genetic and clinical findings in 19 unrelated BCD patients recruited from five international retinal dystrophy clinics. Patients underwent ophthalmic examinations and were screened for <italic>CYP4V2</italic> mutations by Sanger sequencing and quantitative polymerase chain reaction (qPCR) copy number variation screening. Eight <italic>CYP4V2</italic> mutations were found in 10/19 patients, including three patients in whom only monoallelic mutations were detected. Four novel mutations were identified: c.604G>A; p.(Glu202Lys), c.242C>G; p.(Thr81Arg), c.604+4A>G; p.(?), and c.1249dup; p.(Thr417Asnfs*2). In addition, we identified a heterozygous paternally inherited genomic deletion of at least 3.8 Mb, encompassing the complete <italic>CYP4V2</italic> gene and several other genes, which is novel. Clinically, patients demonstrated phenotypic variability, predominantly showing choroidal sclerosis, attenuated vessels, and crystalline deposits of varying degrees of severity. To our knowledge, our study reports the first heterozygous <italic>CYP4V2</italic> deletion and hence a novel mutational mechanism underlying BCD. Our results emphasize the importance of copy number screening in BCD. Finally, the identification of <italic>CYP4V2</italic>‐negative patients with indistinguishable phenotypes from <italic>CYP4V2</italic>‐positive patients might suggest the presence of mutations outside the coding regions of <italic>CYP4V2</italic>, or locus heterogeneity, which is unreported so far.</p> </abstract>