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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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Multiple sequenced alignment of bestrophin-1 around the mutated residues for eight species. The amino acids boxed with colors indicate the positions of novel mutations in the present study. Mutations in a heterozygous state were marked with blue, while mutations in a homozygous or compound heterozygous state were marked with orange. These mutations occurred in highly conserved regions.
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f6: Multiple sequenced alignment of bestrophin-1 around the mutated residues for eight species. The amino acids boxed with colors indicate the positions of novel mutations in the present study. Mutations in a heterozygous state were marked with blue, while mutations in a homozygous or compound heterozygous state were marked with orange. These mutations occurred in highly conserved regions.

Mentions: Seven patients from families A–F harbored one heterozygous BEST1 mutation. Based on this finding, along with the typical fundus appearance of BVMD in these patients and the positive family history, an AD inheritance pattern of BVMD was established in these families. Five missense mutations were identified, including two novel mutations (p.T4I and p.A291V) and three reported mutations (p.R218C, p.Q293H, and p.D301G; Table 2). The novel mutations occurred in highly conserved regions (Figure 6).


Screening for BEST1 gene mutations in Chinese patients with bestrophinopathy.

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

Multiple sequenced alignment of bestrophin-1 around the mutated residues for eight species. The amino acids boxed with colors indicate the positions of novel mutations in the present study. Mutations in a heterozygous state were marked with blue, while mutations in a homozygous or compound heterozygous state were marked with orange. These mutations occurred in highly conserved regions.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f6: Multiple sequenced alignment of bestrophin-1 around the mutated residues for eight species. The amino acids boxed with colors indicate the positions of novel mutations in the present study. Mutations in a heterozygous state were marked with blue, while mutations in a homozygous or compound heterozygous state were marked with orange. These mutations occurred in highly conserved regions.
Mentions: Seven patients from families A–F harbored one heterozygous BEST1 mutation. Based on this finding, along with the typical fundus appearance of BVMD in these patients and the positive family history, an AD inheritance pattern of BVMD was established in these families. Five missense mutations were identified, including two novel mutations (p.T4I and p.A291V) and three reported mutations (p.R218C, p.Q293H, and p.D301G; Table 2). The novel mutations occurred in highly conserved regions (Figure 6).

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