Lu Tian1, Tengyang Sun1, Ke Xu1, Xiaohui Zhang1, Xiaoyan Peng1, Yang Li1. 1. Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Sciences Key Laboratory, Beijing, China.
Abstract
Purpose: Mutations in the BEST1 gene can cause Best vitelliform macular dystrophy (BVMD) and autosomal recessive bestrophinopathy (ARB). The aim of the current study was to establish the BEST1 mutation spectrum in Chinese patients with BVMD and ARB and to describe the phenotypic characteristics of patients carrying BEST1 mutations. Methods: A total of 37 probands with a clinical diagnosis of BVMD (17 patients) or ARB (20 patients) were recruited for genetic analysis; of these, only 5 probands had a family history. All probands underwent detailed ophthalmic examinations. All coding exons and exon-intron boundaries of the BEST1 gene were screened by PCR-based DNA sequencing. In silico programs were used to analyze the pathogenicity of all the variants. Genomic DNA rearrangements of the BEST1 gene were identified by real-time quantitative PCR (RQ-PCR). Results: For patients with BVMD, single heterozygous BEST1 mutations were identified in 13 patients and compound heterozygous mutations were found in 3 patients. For patients with ARB, biallelic mutations were found in 13 probands and single mutant alleles in six patients. Overall, 36 disease-causing variants (20 novel mutations) of the BEST1 gene were identified, including 28 (77.8%) missense, 3 (8.3%) nonsense, 4 (11.1%) splicing effect, and 1 (2.8%) frameshift small duplication mutations. Conclusions: The mutation spectrum of the BEST1 gene in Chinese patients differed from those of Caucasian patients. Mutations that cause ARB differ from those that cause BVMD. BEST1 screening is important for precise diagnosis of BVMD or ARB.
Purpose: Mutations in the BEST1 gene can cause Best vitelliform macular dystrophy (BVMD) and autosomal recessive bestrophinopathy (ARB). The aim of the current study was to establish the BEST1 mutation spectrum in Chinese patients with BVMD and ARB and to describe the phenotypic characteristics of patients carrying BEST1 mutations. Methods: A total of 37 probands with a clinical diagnosis of BVMD (17 patients) or ARB (20 patients) were recruited for genetic analysis; of these, only 5 probands had a family history. All probands underwent detailed ophthalmic examinations. All coding exons and exon-intron boundaries of the BEST1 gene were screened by PCR-based DNA sequencing. In silico programs were used to analyze the pathogenicity of all the variants. Genomic DNA rearrangements of the BEST1 gene were identified by real-time quantitative PCR (RQ-PCR). Results: For patients with BVMD, single heterozygous BEST1 mutations were identified in 13 patients and compound heterozygous mutations were found in 3 patients. For patients with ARB, biallelic mutations were found in 13 probands and single mutant alleles in six patients. Overall, 36 disease-causing variants (20 novel mutations) of the BEST1 gene were identified, including 28 (77.8%) missense, 3 (8.3%) nonsense, 4 (11.1%) splicing effect, and 1 (2.8%) frameshift small duplication mutations. Conclusions: The mutation spectrum of the BEST1 gene in Chinese patients differed from those of Caucasian patients. Mutations that cause ARB differ from those that cause BVMD. BEST1 screening is important for precise diagnosis of BVMD or ARB.
Authors: Lama Jaffal; Wissam H Joumaa; Alexandre Assi; Charles Helou; Christel Condroyer; Maya El Dor; Georges Cherfan; Christina Zeitz; Isabelle Audo; Kazem Zibara; Said El Shamieh Journal: Genes (Basel) Date: 2019-02-18 Impact factor: 4.096
Authors: Imen Habibi; Yosra Falfoul; Margarita G Todorova; Stefan Wyrsch; Veronika Vaclavik; Maria Helfenstein; Ahmed Turki; Khaled El Matri; Leila El Matri; Daniel F Schorderet Journal: Genes (Basel) Date: 2019-11-21 Impact factor: 4.096
Authors: Karsten Hufendiek; Katerina Hufendiek; Herbert Jägle; Heidi Stöhr; Marius Book; Georg Spital; Günay Rustambayova; Carsten Framme; Bernhard H F Weber; Agnes B Renner; Ulrich Kellner Journal: Int J Mol Sci Date: 2020-12-08 Impact factor: 5.923
Authors: Hae Rang Kim; Jinu Han; Yong Joon Kim; Hyun Goo Kang; Suk Ho Byeon; Sung Soo Kim; Christopher Seungkyu Lee Journal: Genes (Basel) Date: 2022-07-04 Impact factor: 4.141