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Screening for BEST1 gene mutations in Chinese patients with bestrophinopathy.

Tian R, Yang G, Wang J, Chen Y - Mol. Vis. (2014)

Bottom Line: Patients with biallelic BEST1 mutations were common among Chinese patients with bestrophinopathy, and the phenotypes varied.The features and combinations of different BEST1 mutations as well as epistatic effects may influence phenotype expression.Our results expand the BEST1 mutation spectrum.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, China;

ABSTRACT

Purpose: The purpose of this study was to analyze BEST1 gene mutations in Chinese patients with bestrophinopathy and to describe the clinical features of these patients.

Methods: Thirteen patients from 12 unrelated Chinese families affected by bestrophinopathy were recruited and clinically evaluated with best-corrected visual acuity examination, slit-lamp biomicroscopy, fundus examination and photography, optical coherence tomography, fundus autofluorescence, electro-oculography, and electroretinography. Blood samples were collected for DNA extraction. Mutation analysis was performed by direct sequencing of the BEST1 gene. One hundred control chromosomes were also screened to exclude nonpathogenic polymorphisms.

Results: Seven patients showed clinical pictures of Best vitelliform macular dystrophy (BVMD) and harbored heterozygous mutations compatible with autosomal dominant inheritance. Two novel mutations (p.T4I and p.A291V) and three reported mutations (p.R218C, p.Q293H, and p.D301G) were identified. Six patients carried BEST1 mutations on both alleles compatible with autosomal recessive inheritance. Compound heterozygous mutations were detected in four patients who presented a BVMD phenotype, while homozygous mutations were detected in two patients with autosomal recessive bestrophinopathy. Mutation analysis revealed eight mutations. Four (p.Y33H, p.R130L, p.M163R, and c.519delA) were novel, and four (p.R13H, p.A195V, p.R255W, and p.W287*) had previously been reported.

Conclusions: Patients with biallelic BEST1 mutations were common among Chinese patients with bestrophinopathy, and the phenotypes varied. The features and combinations of different BEST1 mutations as well as epistatic effects may influence phenotype expression. Our results expand the BEST1 mutation spectrum.

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Related in: MedlinePlus

Clinical evaluation of patient II:1/family H with homozygous mutation p.R130L. A, B: Fundus photography revealed a cystoid macular lesion and multiple yellowish subretinal deposits throughout the posterior pole in both eyes. C, D: OCT showed bilateral marked intraretinal cysts in the macula and neurosensory retina detachment. OD, right eye; OS, left eye.
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f5: Clinical evaluation of patient II:1/family H with homozygous mutation p.R130L. A, B: Fundus photography revealed a cystoid macular lesion and multiple yellowish subretinal deposits throughout the posterior pole in both eyes. C, D: OCT showed bilateral marked intraretinal cysts in the macula and neurosensory retina detachment. OD, right eye; OS, left eye.

Mentions: Ophthalmologic examinations of patients from families G–H, however, revealed different clinical pictures. The proband of family G (patient II:1) was a 6-year-old boy with a history of macular dystrophy and reduced vision, and his BCVA was 20/200 in the right eye and 20/63 in the left eye at diagnosis. Fundus examination showed subretinal fibrosis in the fovea of the left eye and in the temporal area of both eyes. Multiple yellowish deposits were present in the left eye. OCT demonstrated intraretinal cysts and neurosensory retinal detachment in both eyes. The FAF image showed multiple hyper-autofluorescent lesions in the peripheral retina due to deposits (Figure 4). ERG examination revealed reduced amplitudes of scotopic and photopic full-field ERG responses. The Arden ratio of EOG was 0.95 OD and 1.18 OS. The proband of family H (patient II:1) was referred to Peking Union Medical College Hospital in 2011 at age 23 years with a complaint of decreased vision in both eyes. At examination, BCVA was 20/63 in the right eye and 20/200 in the left eye. Fundus photography revealed a cystoid macular lesion and dozens of round, yellowish, subretinal deposits throughout the posterior pole in both eyes. OCT showed marked intraretinal cystoid fluid collection in the macula and neurosensory retina detachment in both eyes (Figure 5). The amplitudes of the scotopic and photopic full-field ERG responses were decreased. The Arden ratio of EOG was 1.11 OD and 1.23 OS. Based on these findings, the two patients were clinically diagnosed with ARB. Their parents showed no clinical signs of the disease.


Screening for BEST1 gene mutations in Chinese patients with bestrophinopathy.

Tian R, Yang G, Wang J, Chen Y - Mol. Vis. (2014)

Clinical evaluation of patient II:1/family H with homozygous mutation p.R130L. A, B: Fundus photography revealed a cystoid macular lesion and multiple yellowish subretinal deposits throughout the posterior pole in both eyes. C, D: OCT showed bilateral marked intraretinal cysts in the macula and neurosensory retina detachment. OD, right eye; OS, left eye.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4225144&req=5

f5: Clinical evaluation of patient II:1/family H with homozygous mutation p.R130L. A, B: Fundus photography revealed a cystoid macular lesion and multiple yellowish subretinal deposits throughout the posterior pole in both eyes. C, D: OCT showed bilateral marked intraretinal cysts in the macula and neurosensory retina detachment. OD, right eye; OS, left eye.
Mentions: Ophthalmologic examinations of patients from families G–H, however, revealed different clinical pictures. The proband of family G (patient II:1) was a 6-year-old boy with a history of macular dystrophy and reduced vision, and his BCVA was 20/200 in the right eye and 20/63 in the left eye at diagnosis. Fundus examination showed subretinal fibrosis in the fovea of the left eye and in the temporal area of both eyes. Multiple yellowish deposits were present in the left eye. OCT demonstrated intraretinal cysts and neurosensory retinal detachment in both eyes. The FAF image showed multiple hyper-autofluorescent lesions in the peripheral retina due to deposits (Figure 4). ERG examination revealed reduced amplitudes of scotopic and photopic full-field ERG responses. The Arden ratio of EOG was 0.95 OD and 1.18 OS. The proband of family H (patient II:1) was referred to Peking Union Medical College Hospital in 2011 at age 23 years with a complaint of decreased vision in both eyes. At examination, BCVA was 20/63 in the right eye and 20/200 in the left eye. Fundus photography revealed a cystoid macular lesion and dozens of round, yellowish, subretinal deposits throughout the posterior pole in both eyes. OCT showed marked intraretinal cystoid fluid collection in the macula and neurosensory retina detachment in both eyes (Figure 5). The amplitudes of the scotopic and photopic full-field ERG responses were decreased. The Arden ratio of EOG was 1.11 OD and 1.23 OS. Based on these findings, the two patients were clinically diagnosed with ARB. Their parents showed no clinical signs of the disease.

Bottom Line: Patients with biallelic BEST1 mutations were common among Chinese patients with bestrophinopathy, and the phenotypes varied.The features and combinations of different BEST1 mutations as well as epistatic effects may influence phenotype expression.Our results expand the BEST1 mutation spectrum.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, China;

ABSTRACT

Purpose: The purpose of this study was to analyze BEST1 gene mutations in Chinese patients with bestrophinopathy and to describe the clinical features of these patients.

Methods: Thirteen patients from 12 unrelated Chinese families affected by bestrophinopathy were recruited and clinically evaluated with best-corrected visual acuity examination, slit-lamp biomicroscopy, fundus examination and photography, optical coherence tomography, fundus autofluorescence, electro-oculography, and electroretinography. Blood samples were collected for DNA extraction. Mutation analysis was performed by direct sequencing of the BEST1 gene. One hundred control chromosomes were also screened to exclude nonpathogenic polymorphisms.

Results: Seven patients showed clinical pictures of Best vitelliform macular dystrophy (BVMD) and harbored heterozygous mutations compatible with autosomal dominant inheritance. Two novel mutations (p.T4I and p.A291V) and three reported mutations (p.R218C, p.Q293H, and p.D301G) were identified. Six patients carried BEST1 mutations on both alleles compatible with autosomal recessive inheritance. Compound heterozygous mutations were detected in four patients who presented a BVMD phenotype, while homozygous mutations were detected in two patients with autosomal recessive bestrophinopathy. Mutation analysis revealed eight mutations. Four (p.Y33H, p.R130L, p.M163R, and c.519delA) were novel, and four (p.R13H, p.A195V, p.R255W, and p.W287*) had previously been reported.

Conclusions: Patients with biallelic BEST1 mutations were common among Chinese patients with bestrophinopathy, and the phenotypes varied. The features and combinations of different BEST1 mutations as well as epistatic effects may influence phenotype expression. Our results expand the BEST1 mutation spectrum.

Show MeSH
Related in: MedlinePlus