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Spectrum of rhodopsin mutations in Korean patients with retinitis pigmentosa.

Kim KJ, Kim C, Bok J, Kim KS, Lee EJ, Park SP, Chung H, Han BG, Kim HL, Kimm K, Yu HG, Lee JY - Mol. Vis. (2011)

Bottom Line: The allele frequency of missense mutations was measured in 114 ethnically matched controls. p.A298D, newly identified in a sporadic patient, had never been found in controls and was predicted to be pathogenic.The results reveal the spectrum of RHO mutations in Korean RP patients and clinical features that vary according to mutations.Our findings will be useful for understanding these genetic spectra and the genotype-phenotype correlations and will therefore help with predicting disease prognosis and facilitating the development of gene therapy.

View Article: PubMed Central - PubMed

Affiliation: Center for Genome Science, National Institute of Health, Chungcheongbuk-do, Korea.

ABSTRACT

Purpose: To determine the spectrum and frequency of rhodopsin gene (RHO) mutations in Korean patients with retinitis pigmentosa (RP) and to characterize genotype-phenotype correlations in patients with mutations.

Methods: The RHO mutations were screened by direct sequencing, and mutation prevalence was measured in patients and controls. The impact of missense mutations to RP was predicted by segregation analysis, peptide sequence alignment, and in silico analysis. The severity of disease in patients with the missense mutations was compared by visual acuity, electroretinography, optical coherence tomography, and kinetic visual field testing.

Results: Five heterozygous mutations were identified in six of 302 probands with RP, including a novel mutation (c.893C>A, p.A298D) and four known mutations (c.50C>T, p.T17M; c.533A>G, p.Y178C; c.888G>T, p.K296N; and c.1040C>T, p.P347L). The allele frequency of missense mutations was measured in 114 ethnically matched controls. p.A298D, newly identified in a sporadic patient, had never been found in controls and was predicted to be pathogenic. Among the patients with the missense mutations, we observed the most severe phenotype in patients with p.P347L, less severe phenotypes in patients with p.Y178C or p.A298D, and a relatively moderate phenotype in a patient with p.T17M.

Conclusions: The results reveal the spectrum of RHO mutations in Korean RP patients and clinical features that vary according to mutations. Our findings will be useful for understanding these genetic spectra and the genotype-phenotype correlations and will therefore help with predicting disease prognosis and facilitating the development of gene therapy.

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Related in: MedlinePlus

Pedigrees of families in which a rhodopsin mutation was identified. The mutation p.Y178C (B) and the mutation p.P347L (E) were segregated with disease phenotype. The newly identified mutation p.A298D (D) was found in a sporadic patient (II-3). Black and white symbols indicate affected and unaffected individuals, respectively. The mutation is represented by “m”; wild-type alleles are represented by “+”; arrows indicate probands.
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f1: Pedigrees of families in which a rhodopsin mutation was identified. The mutation p.Y178C (B) and the mutation p.P347L (E) were segregated with disease phenotype. The newly identified mutation p.A298D (D) was found in a sporadic patient (II-3). Black and white symbols indicate affected and unaffected individuals, respectively. The mutation is represented by “m”; wild-type alleles are represented by “+”; arrows indicate probands.

Mentions: A total of 302 probands from Korean families with RP were screened for mutations in RHO. By sequencing the exons and flanking intronic regions, five heterozygous mutations (c.50C>T, p.T17M; c.533A>G, p.Y178C; c.888G>T, p.K296N; c.893C>A, p.A298D; and c.1040C>T, p.P347L) were identified in six probands and were absent in 114 controls (Table 2). Of these, p.A298D has not been reported previously. The mutation frequencies were 10.5% (four mutation carriers in 38 patients, 4/38) for adRP, 1.1% (2/182) for sporadic RP, and 2.0% (6/302) in total. No mutation was detected in families with arRP and unknown patterns of inheritance. Mutations p.Y178C and p.P347L segregated with disease phenotype in studied families (Figure 1).


Spectrum of rhodopsin mutations in Korean patients with retinitis pigmentosa.

Kim KJ, Kim C, Bok J, Kim KS, Lee EJ, Park SP, Chung H, Han BG, Kim HL, Kimm K, Yu HG, Lee JY - Mol. Vis. (2011)

Pedigrees of families in which a rhodopsin mutation was identified. The mutation p.Y178C (B) and the mutation p.P347L (E) were segregated with disease phenotype. The newly identified mutation p.A298D (D) was found in a sporadic patient (II-3). Black and white symbols indicate affected and unaffected individuals, respectively. The mutation is represented by “m”; wild-type alleles are represented by “+”; arrows indicate probands.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3113629&req=5

f1: Pedigrees of families in which a rhodopsin mutation was identified. The mutation p.Y178C (B) and the mutation p.P347L (E) were segregated with disease phenotype. The newly identified mutation p.A298D (D) was found in a sporadic patient (II-3). Black and white symbols indicate affected and unaffected individuals, respectively. The mutation is represented by “m”; wild-type alleles are represented by “+”; arrows indicate probands.
Mentions: A total of 302 probands from Korean families with RP were screened for mutations in RHO. By sequencing the exons and flanking intronic regions, five heterozygous mutations (c.50C>T, p.T17M; c.533A>G, p.Y178C; c.888G>T, p.K296N; c.893C>A, p.A298D; and c.1040C>T, p.P347L) were identified in six probands and were absent in 114 controls (Table 2). Of these, p.A298D has not been reported previously. The mutation frequencies were 10.5% (four mutation carriers in 38 patients, 4/38) for adRP, 1.1% (2/182) for sporadic RP, and 2.0% (6/302) in total. No mutation was detected in families with arRP and unknown patterns of inheritance. Mutations p.Y178C and p.P347L segregated with disease phenotype in studied families (Figure 1).

Bottom Line: The allele frequency of missense mutations was measured in 114 ethnically matched controls. p.A298D, newly identified in a sporadic patient, had never been found in controls and was predicted to be pathogenic.The results reveal the spectrum of RHO mutations in Korean RP patients and clinical features that vary according to mutations.Our findings will be useful for understanding these genetic spectra and the genotype-phenotype correlations and will therefore help with predicting disease prognosis and facilitating the development of gene therapy.

View Article: PubMed Central - PubMed

Affiliation: Center for Genome Science, National Institute of Health, Chungcheongbuk-do, Korea.

ABSTRACT

Purpose: To determine the spectrum and frequency of rhodopsin gene (RHO) mutations in Korean patients with retinitis pigmentosa (RP) and to characterize genotype-phenotype correlations in patients with mutations.

Methods: The RHO mutations were screened by direct sequencing, and mutation prevalence was measured in patients and controls. The impact of missense mutations to RP was predicted by segregation analysis, peptide sequence alignment, and in silico analysis. The severity of disease in patients with the missense mutations was compared by visual acuity, electroretinography, optical coherence tomography, and kinetic visual field testing.

Results: Five heterozygous mutations were identified in six of 302 probands with RP, including a novel mutation (c.893C>A, p.A298D) and four known mutations (c.50C>T, p.T17M; c.533A>G, p.Y178C; c.888G>T, p.K296N; and c.1040C>T, p.P347L). The allele frequency of missense mutations was measured in 114 ethnically matched controls. p.A298D, newly identified in a sporadic patient, had never been found in controls and was predicted to be pathogenic. Among the patients with the missense mutations, we observed the most severe phenotype in patients with p.P347L, less severe phenotypes in patients with p.Y178C or p.A298D, and a relatively moderate phenotype in a patient with p.T17M.

Conclusions: The results reveal the spectrum of RHO mutations in Korean RP patients and clinical features that vary according to mutations. Our findings will be useful for understanding these genetic spectra and the genotype-phenotype correlations and will therefore help with predicting disease prognosis and facilitating the development of gene therapy.

Show MeSH
Related in: MedlinePlus