Mutational Analysis of theRhodopsinGene in Sector Retinitis Pigmentosa

Maria L. Napier, Dash Durga, Clive J. Wolsley, Sarah Chamney, Sharon Alexander, Rosie Brennan, David A. Simpson, Giuliana Silvestri, Colin Willoughby

    Research output: Contribution to journalArticle

    3 Citations (Scopus)

    Abstract

    BACKGROUND:To determine the role of rhodopsin (RHO) gene mutations in patients with sector retinitis pigmentosa (RP) from Northern Ireland.DESIGN:A case series of sector RP in a tertiary ocular genetics clinic.PARTICIPANTS:Four patients with sector RP were recruited from the Royal Victoria Hospital (Belfast, Northern Ireland) and Altnagelvin Hospital (Londonderry, Northern Ireland) following informed consent.METHODS:The diagnosis of sector RP was based on clinical examination, International Society for Clinical Electrophysiology of Vision (ISCEV) standard electrophysiology, and visual field analysis. DNA was extracted from peripheral blood leucocytes and the coding regions and adjacent flanking intronic sequences of the RHO gene were polymerase chain reaction (PCR) amplified and cycle sequenced.MAIN OUTCOME MEASURE:Rhodopsin mutational status.RESULTS:A heterozygous missense mutation in RHO (c.173C > T) resulting in a non-conservative substitution of threonine to methionine (p. Thr58Met) was identified in one patient and was absent from 360 control individuals. This non-conservative substitution (p.Thr58Met) replaces a highly evolutionary conserved polar hydrophilic threonine residue with a non-polar hydrophobic methionine residue at position 58 near the cytoplasmic border of helix A of RHO.CONCLUSIONS:The study identified a RHO gene mutation (p.Thr58Met) not previously reported in RP in a patient with sector RP. These findings outline the phenotypic variability associated with RHO mutations. It has been proposed that the regional effects of RHO mutations are likely to result from interplay between mutant alleles and other genetic, epigenetic and environmental factors.
    LanguageEnglish
    Pages239-243
    JournalOphthalmic Genetics
    Volume36
    Issue number3
    DOIs
    Publication statusAccepted/In press - 23 Aug 2014

    Fingerprint

    Retinitis Pigmentosa
    Rhodopsin
    Northern Ireland
    Mutation
    Threonine
    Methionine
    Genes
    Victoria
    Electrophysiology
    Missense Mutation
    Visual Fields
    Informed Consent
    Epigenomics
    Leukocytes
    Alleles
    Polymerase Chain Reaction
    DNA

    Keywords

    • Mutation
    • retinitis pigmentosa
    • rhodopsin
    • rod-cone dystrophy
    • sector RP

    Cite this

    Napier, M. L., Durga, D., Wolsley, C. J., Chamney, S., Alexander, S., Brennan, R., ... Willoughby, C. (Accepted/In press). Mutational Analysis of theRhodopsinGene in Sector Retinitis Pigmentosa. Ophthalmic Genetics, 36(3), 239-243. https://doi.org/10.3109/13816810.2014.958862
    Napier, Maria L. ; Durga, Dash ; Wolsley, Clive J. ; Chamney, Sarah ; Alexander, Sharon ; Brennan, Rosie ; Simpson, David A. ; Silvestri, Giuliana ; Willoughby, Colin. / Mutational Analysis of theRhodopsinGene in Sector Retinitis Pigmentosa. In: Ophthalmic Genetics. 2014 ; Vol. 36, No. 3. pp. 239-243.
    @article{c88124e018f84554866583243644f1e7,
    title = "Mutational Analysis of theRhodopsinGene in Sector Retinitis Pigmentosa",
    abstract = "BACKGROUND:To determine the role of rhodopsin (RHO) gene mutations in patients with sector retinitis pigmentosa (RP) from Northern Ireland.DESIGN:A case series of sector RP in a tertiary ocular genetics clinic.PARTICIPANTS:Four patients with sector RP were recruited from the Royal Victoria Hospital (Belfast, Northern Ireland) and Altnagelvin Hospital (Londonderry, Northern Ireland) following informed consent.METHODS:The diagnosis of sector RP was based on clinical examination, International Society for Clinical Electrophysiology of Vision (ISCEV) standard electrophysiology, and visual field analysis. DNA was extracted from peripheral blood leucocytes and the coding regions and adjacent flanking intronic sequences of the RHO gene were polymerase chain reaction (PCR) amplified and cycle sequenced.MAIN OUTCOME MEASURE:Rhodopsin mutational status.RESULTS:A heterozygous missense mutation in RHO (c.173C > T) resulting in a non-conservative substitution of threonine to methionine (p. Thr58Met) was identified in one patient and was absent from 360 control individuals. This non-conservative substitution (p.Thr58Met) replaces a highly evolutionary conserved polar hydrophilic threonine residue with a non-polar hydrophobic methionine residue at position 58 near the cytoplasmic border of helix A of RHO.CONCLUSIONS:The study identified a RHO gene mutation (p.Thr58Met) not previously reported in RP in a patient with sector RP. These findings outline the phenotypic variability associated with RHO mutations. It has been proposed that the regional effects of RHO mutations are likely to result from interplay between mutant alleles and other genetic, epigenetic and environmental factors.",
    keywords = "Mutation, retinitis pigmentosa, rhodopsin, rod-cone dystrophy, sector RP",
    author = "Napier, {Maria L.} and Dash Durga and Wolsley, {Clive J.} and Sarah Chamney and Sharon Alexander and Rosie Brennan and Simpson, {David A.} and Giuliana Silvestri and Colin Willoughby",
    year = "2014",
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    Napier, ML, Durga, D, Wolsley, CJ, Chamney, S, Alexander, S, Brennan, R, Simpson, DA, Silvestri, G & Willoughby, C 2014, 'Mutational Analysis of theRhodopsinGene in Sector Retinitis Pigmentosa', Ophthalmic Genetics, vol. 36, no. 3, pp. 239-243. https://doi.org/10.3109/13816810.2014.958862

    Mutational Analysis of theRhodopsinGene in Sector Retinitis Pigmentosa. / Napier, Maria L.; Durga, Dash; Wolsley, Clive J.; Chamney, Sarah; Alexander, Sharon; Brennan, Rosie; Simpson, David A.; Silvestri, Giuliana; Willoughby, Colin.

    In: Ophthalmic Genetics, Vol. 36, No. 3, 23.08.2014, p. 239-243.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Mutational Analysis of theRhodopsinGene in Sector Retinitis Pigmentosa

    AU - Napier, Maria L.

    AU - Durga, Dash

    AU - Wolsley, Clive J.

    AU - Chamney, Sarah

    AU - Alexander, Sharon

    AU - Brennan, Rosie

    AU - Simpson, David A.

    AU - Silvestri, Giuliana

    AU - Willoughby, Colin

    PY - 2014/8/23

    Y1 - 2014/8/23

    N2 - BACKGROUND:To determine the role of rhodopsin (RHO) gene mutations in patients with sector retinitis pigmentosa (RP) from Northern Ireland.DESIGN:A case series of sector RP in a tertiary ocular genetics clinic.PARTICIPANTS:Four patients with sector RP were recruited from the Royal Victoria Hospital (Belfast, Northern Ireland) and Altnagelvin Hospital (Londonderry, Northern Ireland) following informed consent.METHODS:The diagnosis of sector RP was based on clinical examination, International Society for Clinical Electrophysiology of Vision (ISCEV) standard electrophysiology, and visual field analysis. DNA was extracted from peripheral blood leucocytes and the coding regions and adjacent flanking intronic sequences of the RHO gene were polymerase chain reaction (PCR) amplified and cycle sequenced.MAIN OUTCOME MEASURE:Rhodopsin mutational status.RESULTS:A heterozygous missense mutation in RHO (c.173C > T) resulting in a non-conservative substitution of threonine to methionine (p. Thr58Met) was identified in one patient and was absent from 360 control individuals. This non-conservative substitution (p.Thr58Met) replaces a highly evolutionary conserved polar hydrophilic threonine residue with a non-polar hydrophobic methionine residue at position 58 near the cytoplasmic border of helix A of RHO.CONCLUSIONS:The study identified a RHO gene mutation (p.Thr58Met) not previously reported in RP in a patient with sector RP. These findings outline the phenotypic variability associated with RHO mutations. It has been proposed that the regional effects of RHO mutations are likely to result from interplay between mutant alleles and other genetic, epigenetic and environmental factors.

    AB - BACKGROUND:To determine the role of rhodopsin (RHO) gene mutations in patients with sector retinitis pigmentosa (RP) from Northern Ireland.DESIGN:A case series of sector RP in a tertiary ocular genetics clinic.PARTICIPANTS:Four patients with sector RP were recruited from the Royal Victoria Hospital (Belfast, Northern Ireland) and Altnagelvin Hospital (Londonderry, Northern Ireland) following informed consent.METHODS:The diagnosis of sector RP was based on clinical examination, International Society for Clinical Electrophysiology of Vision (ISCEV) standard electrophysiology, and visual field analysis. DNA was extracted from peripheral blood leucocytes and the coding regions and adjacent flanking intronic sequences of the RHO gene were polymerase chain reaction (PCR) amplified and cycle sequenced.MAIN OUTCOME MEASURE:Rhodopsin mutational status.RESULTS:A heterozygous missense mutation in RHO (c.173C > T) resulting in a non-conservative substitution of threonine to methionine (p. Thr58Met) was identified in one patient and was absent from 360 control individuals. This non-conservative substitution (p.Thr58Met) replaces a highly evolutionary conserved polar hydrophilic threonine residue with a non-polar hydrophobic methionine residue at position 58 near the cytoplasmic border of helix A of RHO.CONCLUSIONS:The study identified a RHO gene mutation (p.Thr58Met) not previously reported in RP in a patient with sector RP. These findings outline the phenotypic variability associated with RHO mutations. It has been proposed that the regional effects of RHO mutations are likely to result from interplay between mutant alleles and other genetic, epigenetic and environmental factors.

    KW - Mutation

    KW - retinitis pigmentosa

    KW - rhodopsin

    KW - rod-cone dystrophy

    KW - sector RP

    U2 - 10.3109/13816810.2014.958862

    DO - 10.3109/13816810.2014.958862

    M3 - Article

    VL - 36

    SP - 239

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    JO - Ophthalmic Genetics

    T2 - Ophthalmic Genetics

    JF - Ophthalmic Genetics

    SN - 1381-6810

    IS - 3

    ER -

    Napier ML, Durga D, Wolsley CJ, Chamney S, Alexander S, Brennan R et al. Mutational Analysis of theRhodopsinGene in Sector Retinitis Pigmentosa. Ophthalmic Genetics. 2014 Aug 23;36(3):239-243. https://doi.org/10.3109/13816810.2014.958862