Abstract
To identify Bestrophin 1 (BEST1) causative mutations in six Lebanese patients from three families, of whom four had a presumed clinical diagnosis of autosomal recessive bestrophinopathy (ARB) and two showed a phenotype with a single vitelliform lesion, patients were subjected to standard ophthalmic examinations. In addition, BEST1 exons and their flanking regions were amplified and sequenced by Sanger sequencing. Co-segregation and detailed bio-informatic analyses were performed. Clinical examination results were consistent with ARB diagnosis for all index patients showing multifocal vitelliform lesions and a markedly reduced light peak in the electrooculogram, including the two patients with a single vitelliform lesion. In all cases, most likely disease-causing BEST1 mutations co-segregated with the phenotype. The ARB cases showed homozygous missense variants (M1, c.209A>G, p.(Asp70Gly) in exon 3, M2, c.1403C>T; p.(Pro468Leu) in exon 10 and M3, c.830C>T, p.(Thr277Met) in exon 7), while the two patients with a single vitelliform lesion were compound heterozygous for M1 and M2. To our knowledge, this is the first study describing mutations in Lebanese patients with bestrophinopathy, where novel biallelic BEST1 mutations associated with two phenotypes were identified. Homozygous mutations were associated with multifocal lesions, subretinal fluid, and intraretinal cysts, whereas compound heterozygous ones were responsible for a single macular vitelliform lesion.
Highlights
Human Bestrophin 1 (BEST1) (OMIM 607854), previously known as VMD2, is localized on chromosome 11q12.3 and consists of 11 exons [1,2]
Along with bestrophinopathies, mutated BEST1 was reported in patients with retinitis pigmentosa-50 (RP50; OMIM 613194) [10]
We aimed to identify causative BEST1 mutations in six Lebanese patients from three families with a presumed diagnosis of autosomal recessive bestrophinopathy (ARB) and showing two phenotypes; one with multifocal lesions, the other with a single macular vitelliform lesion
Summary
Human Bestrophin 1 (BEST1) (OMIM 607854), previously known as VMD2, is localized on chromosome 11q12.3 and consists of 11 exons [1,2]. Leroy (2012) commented that the phenotypes of the patients reported by Davidson et al (2009) were all labeled “retinitis pigmentosa” initially, the illustrations of the retinal phenotypes in the paper were highly suggestive of either autosomal dominant vitreoretinochoroidopathy (193220) or ARB (611809) [11] The hallmark of these BEST1-related dystrophies is a severely reduced electro-oculorgam (EOG) light rise with no or minimal to mild full-field electroretinogram (ERG) abnormalities in keeping with primary RPE dysfunction. Patients with ARB show a severe reduction in the EOG light rise similar to that seen in both BVMD and ADVIRC [9] They show multifocal vitelliform lesions, with subretinal fluid and intraretinal cysts, scattered over the posterior pole of the retina [9].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
