Mutation analysis of<i>BEST1</i>in Japanese patients with Best's vitelliform macular dystrophy

Katagiri, Satoshi; Hayashi, Takaaki; Ohkuma, Yasuhiro; Sekiryu, Tetsuju; Takeuchi, Tomokazu; Gekka, Tamaki; Kondo, Mineo; Iwata, Takeshi; Tsuneoka, Hiroshi

doi:10.1136/bjophthalmol-2015-306830

Cited by 20 publications

(14 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…4 ). The first mutation we identified has previously been reported in Japanese patients ( 14 ). Since we were unable to obtain information of the patient's parents, we could not determine the inheritance pattern of the mutations.…”

Section: Resultsmentioning

confidence: 89%

Two heterozygous mutations identified in one Chinese patient with bilateral macular coloboma

Gao

Chen

et al. 2017

Molecular Medicine Reports

View full text Add to dashboard Cite

Congenital macular coloboma is characterized by defined punched out atrophic lesions of the macula. The present study aimed to investigate the genetic alterations of one Chinese sporadic patient with bilateral large macular coloboma. Complete ophthalmic examinations, including best-corrected visual acuity, slit-lamp examination, fundus examination, fundus photograph and fundus fluorescein angiography imaging, Pentacam, and optical coherence tomography were performed on the patient. Genomic DNA was extracted from leukocytes in a peripheral blood sample collected from the patient, the patient's unaffected family members and from 200 unrelated control subjects from the same population. Next-generation sequencing of the known genes involved in ocular disease was performed. The functional effects of the mutation were analyzed using Polymorphism Phenotyping (PolyPhen) and Sorting Intolerant From Tolerant (SIFT). One heterozygous bestrophin 1 (BEST1) mutation c.1037C>A (p.Pro346His, p.P346H) in exon 9 and one heterozygous regulating synaptic membrane exocytosis 1 (RIMS1) mutation c.3481A>G (p.Arg1161Gly, p.R1161G) in exon 23 were identified in the patient being investigated, but not in the unaffected family members or unrelated control subjects. Polyphen and SIFT predicted that the amino acid substitution p.P346H in the BEST1 protein is damaging. In addition, Polyphen predicted that the amino acid substitution p.R1161G in the RIM1 protein is damaging. The results of the current study have increased the mutation spectrums of BEST1 and RIMS1, and are valuable for improving the current genetic counseling process and developing novel therapeutic interventions for patients with macular coloboma.

show abstract

Section: Resultsmentioning

confidence: 89%

Two heterozygous mutations identified in one Chinese patient with bilateral macular coloboma

Gao

Chen

et al. 2017

Molecular Medicine Reports

View full text Add to dashboard Cite

show abstract

“…The mutation p.A195V is one of the most prevalent mutations among those patients with biallelic mutations, 32 and the patients carrying the heterozygous mutation p.A195V compounded with another heterozygous mutation exhibited either a phenotype of BVMD or of ARB, whereas the individuals carrying the heterozygous mutation p.A195V alone did not shown any phenotype of BVMD or ARB. 15,23,32 In the current study, the mutation p.R25W was identified in two ARB patients in the compound heterozygous state (one coupled with a synonymous change c.763C>A and another one with a variant c.*24C>T). The father of proband 010397 carrying the mutation c.*24C>T was healthy, both clinically and electrophysiologically, whereas her mother, who harbored the mutation p.R25W, had an abnormal EOG (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…The mutation p.S7N in a compound heterozygous state was first identified in a Japanese patient who also showed a typical BVMD phenotype. 23 A heterozygous p.R13H was first reported in a Caucasian patient with a BVMD phenotype; however, the patient had no well-described clinical features and no cosegregation analysis was conducted for this family. 11 In the current study, the patient harboring the compound heterozygous mutations p.S7N/p.R13H exhibited a BVMD phenotype (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…In total, we identified 36 distinct disease-causing variants of the BEST1 gene in this cohort, which included missense (28/36, 77.8%), splicing effect (4/36, 11.1%), nonsense (3/36, 8.3%), and frameshift small duplication (1/ 36, 2.8%) mutations (Supplementary Table S3). [23][24][25][26][27][28] The RQ-PCR analysis revealed no large deletions or insertions of the BEST1 gene in eight patients.…”

Section: Best1 Mutationsmentioning

confidence: 99%

See 1 more Smart Citation

Screening of BEST1 Gene in a Chinese Cohort With Best Vitelliform Macular Dystrophy or Autosomal Recessive Bestrophinopathy

Tian

Sun

et al. 2017

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

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.

show abstract

“…However, the frequency of this mutation is not really known in Caucasian patients and its frequency should be evaluated in larger groups. This mutation is one of the most prevalent mutations among patients with compound mutations and it is associated with either a BVMD or of ARB phenotype, whereas individuals carrying the mutation at a heterozygous state alone did not show any phenotypic features of BVMD or ARB [10][11][12]18,19].…”

Section: Family Cmentioning

confidence: 99%

Clinical and Genetic Findings of Autosomal Recessive Bestrophinopathy (ARB)

Habibi

Falfoul²,

Todorova

et al. 2019

Genes

View full text Add to dashboard Cite

show abstract

Mutation analysis ofBEST1in Japanese patients with Best's vitelliform macular dystrophy

Cited by 20 publications

References 27 publications

Two heterozygous mutations identified in one Chinese patient with bilateral macular coloboma

Two heterozygous mutations identified in one Chinese patient with bilateral macular coloboma

Screening of BEST1 Gene in a Chinese Cohort With Best Vitelliform Macular Dystrophy or Autosomal Recessive Bestrophinopathy

Clinical and Genetic Findings of Autosomal Recessive Bestrophinopathy (ARB)

Contact Info

Product

Resources

About