Clinical and Genetic Findings of Autosomal Recessive Bestrophinopathy (ARB)

Habibi, Imen; Falfoul, Yousra; Todorova, Margarita G.; Wyrsch, Stefan; Vaclavik, Véronika; Helfenstein, Maria; Turki, Ahmed; Matri, Khaled El; Matri, L. El

doi:10.3390/genes10120953

Cited by 18 publications

(13 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Next-generation sequencing genetic analysis of 325 retinal degeneration associated genes was positive for a homozygous mutation in BEST1 , c.103G>A (p.Glu35Lys), which has been previously reported 39 – 41 and predicted to be damaging by Sift, PolyPhen, and CADD.…”

Section: Resultsmentioning

confidence: 81%

“…19,[23][24][25][26][27][28][29][30] Indeed, multiple previous reports of p.Glu35Lys are all associated with autosomal recessive inheritance, without known parent carrier phenotypes. 39,40,41 A major limitation to our study is that parents were not routinely clinically examined in the absence of reported symptoms or a concerning vision history. In rare cases, pathogenic BEST1 variants are inherited in a semidominant fashion.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Phenotypic and Genetic Spectrum of Autosomal Recessive Bestrophinopathy and Best Vitelliform Macular Dystrophy

Pfister

Zein

Cukras

et al. 2021

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

Autosomal recessive bestrophinopathy (ARB) and vitelliform macular dystrophy (VMD) are distinct phenotypes, typically inherited through recessive and dominant patterns, respectively. Recessively inherited VMD (arVMD) has been reported, suggesting that dominant and recessive BEST1-related retinopathies represent a single disease spectrum. This study compares adVMD, arVMD, and ARB to determine whether a continuum exists and to define clinical and genetic features to aid diagnosis and management. METHODS.One arVMD patient and nine ARB patients underwent standard ophthalmic examination, imaging, electrophysiology, and genetic assessments. A meta-analysis of reported BEST1 variants was compiled, and clinical parameters were analyzed with regard to inheritance and phenotype.RESULTS. Among 10 patients with biallelic BEST1 variants, three novel ARB variants (p.Asp118Ala, p.Leu224Gln, p.Val273del) were discovered. A patient with homozygous p.Glu35Lys was clinically unique, presenting with VMD, including hyperautofluorescence extending beyond the macula, peripheral punctate lesions, and shortened axial-length. A tritan-axis color vision deficit was seen in three of six (50%) of ARB patients. Attempts to distinguish recessively-inherited ARB and dominantly-inherited VMD genotypically, by variant frequency and residue location, did not yield significant differences. Literature meta-analysis with principle component analysis of clinical features demonstrated a spectrum of disease with arVMD falling between adVMD and ARB.CONCLUSIONS. This study suggests that arVMD is part of a continuum of autosomal recessive and dominant BEST1-related retinopathies. Detailed clinical and molecular assessments of this cohort and the literature are corroborated by unsupervised analysis, highlighting the overlapping heterogeneity among BEST1-associated clinical diagnoses. Tritan-axis color vision deficit is a previously unreported finding associated with ARB.

show abstract

Section: Resultsmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Phenotypic and Genetic Spectrum of Autosomal Recessive Bestrophinopathy and Best Vitelliform Macular Dystrophy

Pfister

Zein

Cukras

et al. 2021

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

show abstract

“…variant has previously been reported by Tian et al and Habibi et al, albeit in a homozygous state. [34,35] To the best of our knowledge, ours is the rst study to report this variant in a heterozygous state.…”

Section: Genetic Ndingsmentioning

confidence: 86%

A novel compound heterozygous BEST1 gene mutation in two siblings causing autosomal recessive bestrophinopathy

Haque

Nabi

Ahmad

et al. 2022

Preprint

View full text Add to dashboard Cite

Purpose: To describe the clinical features, imaging characteristics, and genetic test results associated with a novel compound heterozygous mutation of BEST1 gene resulting in an autosomal recessive bestrophinopathy (ARB). Methods: Two siblings underwent a complete ophthalmic examination, including dilated fundus examination, fundus photography, fundus autofluorescence imaging, spectral-domain optical coherence tomography (OCT), fluorescein angiography (FA), electroretinography (ERG), and electrooculography (EOG). A clinical diagnosis of ARB was established based on multimodal retinal imaging. Subsequently, clinical exome sequencing, consisting of a panel of 6670 genes, was carried out to assess genetic alterations in the protein-coding region of the genome of the patients. Results: Two siblings (17-year-old female and 15-year-old male) presented with reduced visual acuity and bilateral symmetrical subretinal deposits of hyperautofluorescent materials in the posterior pole. Spectral-domain OCT demonstrated subretinal fluid accumulation. Clinical exome sequencing revealed two mutations in the protein-coding region of the BEST1 gene, including a novel mutation (R105S), creating aberrant BEST1 variants p.Glu35Lys (E35K) and p.Arg105Ser (R105S) expressing from the canonical BEST1 transcript. Conclusions: We have identified and described the phenotype of a novel BEST1 mutation (R105S) in a heterozygous state along with a previously reported mutation of BEST1 (E35K) causing autosomal recessive bestrophinopathy (ARB).

show abstract

“…Both studies further reinforce the need for increasingly diverse reference genome datasets to more accurately identify and interpret genomic variants in the context of rare disease. Other studies in this issue describe genotypic findings from specific ancestral cohorts, including a large genotypic study from Irish patients [9], descriptions of macular genetic disease associations in defined populations [10,11], and the description of detailed phenotypic presentations associated with specific genetic variants [12,13]. Interestingly, two of the studies in this issue describe findings that the same genetic variant can lead to extreme variability in phenotypic presentation.…”

mentioning

confidence: 99%

Phenotype and Genotype Correlations in Inherited Retinal Diseases: Population-Guided Variant Interpretation, Variable Expressivity and Incomplete Penetrance

Ellingford

Hufnagel

Arno

2020

Genes

View full text Add to dashboard Cite

show abstract

Clinical and Genetic Findings of Autosomal Recessive Bestrophinopathy (ARB)

Abstract: Mutations in BEST1 cause several phenotypes including autosomal dominant (AD) Best vitelliform macular dystrophy type 2 (BVMD), AD vitreo-retino-choroidopathy (ADVIRC), and retinitis pigmentosa-50 (RP50). A rare subtype of Bestrophinopathy exists with biallelic mutations in BEST1.

Cited by 18 publications

References 21 publications

Phenotypic and Genetic Spectrum of Autosomal Recessive Bestrophinopathy and Best Vitelliform Macular Dystrophy

Phenotypic and Genetic Spectrum of Autosomal Recessive Bestrophinopathy and Best Vitelliform Macular Dystrophy

A novel compound heterozygous BEST1 gene mutation in two siblings causing autosomal recessive bestrophinopathy

Phenotype and Genotype Correlations in Inherited Retinal Diseases: Population-Guided Variant Interpretation, Variable Expressivity and Incomplete Penetrance

Contact Info

Product

Resources

About