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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

Pedigrees of the 12 Chinese families included in this study and segregation analysis of the biallelic mutations of the BEST1 gene. Squares represent men, and circles represent women. Solid symbols indicate patients affected with bestrophinopathy. Unfilled symbols represent unaffected family members. A diagonal line indicates a deceased family member. The arrow indicates the proband.
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f1: Pedigrees of the 12 Chinese families included in this study and segregation analysis of the biallelic mutations of the BEST1 gene. Squares represent men, and circles represent women. Solid symbols indicate patients affected with bestrophinopathy. Unfilled symbols represent unaffected family members. A diagonal line indicates a deceased family member. The arrow indicates the proband.

Mentions: Thirteen patients diagnosed with bestrophinopathy from 12 independent pedigrees were recruited from the Department of Ophthalmology, Peking Union Medical College Hospital (Figure 1). Detailed ophthalmic examinations were conducted on all subjects, including best-corrected visual acuity (BCVA), slit-lamp biomicroscopy, fundus examination and photography, optical coherence tomography (OCT), fundus autofluorescence (FAF), EOG, and ERG. The fundus images and OCT images were in most cases taken with Topcon-3D OCT-1000 (Topcon Medical Systems, Tokyo, Japan), and FAF examinations were performed with the Spectralis HRA-OCT produced by Heidelberg Engineering (Heidelberg, Germany). EOG and ERG (RetiPort ERG system; Roland Consult, Wiesbaden, Germany) were performed according to the International Society for Clinical Electrophysiology of Vision (ISCEV) standards [20,21].


Screening for BEST1 gene mutations in Chinese patients with bestrophinopathy.

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

Pedigrees of the 12 Chinese families included in this study and segregation analysis of the biallelic mutations of the BEST1 gene. Squares represent men, and circles represent women. Solid symbols indicate patients affected with bestrophinopathy. Unfilled symbols represent unaffected family members. A diagonal line indicates a deceased family member. The arrow indicates the proband.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1: Pedigrees of the 12 Chinese families included in this study and segregation analysis of the biallelic mutations of the BEST1 gene. Squares represent men, and circles represent women. Solid symbols indicate patients affected with bestrophinopathy. Unfilled symbols represent unaffected family members. A diagonal line indicates a deceased family member. The arrow indicates the proband.
Mentions: Thirteen patients diagnosed with bestrophinopathy from 12 independent pedigrees were recruited from the Department of Ophthalmology, Peking Union Medical College Hospital (Figure 1). Detailed ophthalmic examinations were conducted on all subjects, including best-corrected visual acuity (BCVA), slit-lamp biomicroscopy, fundus examination and photography, optical coherence tomography (OCT), fundus autofluorescence (FAF), EOG, and ERG. The fundus images and OCT images were in most cases taken with Topcon-3D OCT-1000 (Topcon Medical Systems, Tokyo, Japan), and FAF examinations were performed with the Spectralis HRA-OCT produced by Heidelberg Engineering (Heidelberg, Germany). EOG and ERG (RetiPort ERG system; Roland Consult, Wiesbaden, Germany) were performed according to the International Society for Clinical Electrophysiology of Vision (ISCEV) standards [20,21].

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