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Phenocopy of a heterozygous carrier of X-linked retinitis pigmentosa due to mosaicism for a RHO variant

Ine Strubbe (UGent) , Caroline Van Cauwenbergh (UGent) , Julie De Zaeytijd (UGent) , Sarah De Jaegere (UGent) , Marieke De Bruyne (UGent) , Toon Rosseel (UGent) , Stijn Van de Sompele (UGent) , Elfride De Baere (UGent) and Bart Leroy (UGent)
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Abstract
We describe both phenotype and pathogenesis in two male siblings with typical retinitis pigmentosa (RP) and the potentially X-linked RP (XLRP) carrier phenotype in their mother. Two affected sons, two unaffected daughters, and their mother underwent detailed ophthalmological assessments including Goldmann perimetry, color vision testing, multimodal imaging and ISCEV-standard electroretinography. Genetic testing consisted of targeted next-generation sequencing (NGS) of known XLRP genes and whole exome sequencing (WES) of known inherited retinal disease genes (RetNet-WES). Variant validation and segregation analysis were performed by Sanger sequencing. The mutational load of the RHO variant in the mother was assessed in DNA from leucocytes, buccal cells and hair follicles using targeted NGS. Both affected sons showed signs of classical RP, while the mother displayed patches of hyperautofluorescence on blue light autofluorescence imaging and regional, intraretinal, spicular pigmentation, reminiscent of a carrier phenotype of XLRP. XLRP testing was negative. RetNet-WES testing revealed RHO variant c.404G>C p.(Arg135Pro) in a mosaic state (21% of the reads) in the mother and in a heterozygous state in both sons. Targeted NGQSS of the RHO variant in different maternal tissues showed a mutation load between 25.06% and 41.72%. We report for the first time that somatic mosaicism of RHO variant c.404G>C p.(Arg135Pro) mimics the phenotype of a female carrier of XLRP, in combination with heterozygosity for the variant in the two affected sons.
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Multidisciplinary

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MLA
Strubbe, Ine, et al. “Phenocopy of a Heterozygous Carrier of X-Linked Retinitis Pigmentosa Due to Mosaicism for a RHO Variant.” SCIENTIFIC REPORTS, vol. 11, 2021, doi:10.1038/s41598-020-80400-3.
APA
Strubbe, I., Van Cauwenbergh, C., De Zaeytijd, J., De Jaegere, S., De Bruyne, M., Rosseel, T., … Leroy, B. (2021). Phenocopy of a heterozygous carrier of X-linked retinitis pigmentosa due to mosaicism for a RHO variant. SCIENTIFIC REPORTS, 11. https://doi.org/10.1038/s41598-020-80400-3
Chicago author-date
Strubbe, Ine, Caroline Van Cauwenbergh, Julie De Zaeytijd, Sarah De Jaegere, Marieke De Bruyne, Toon Rosseel, Stijn Van de Sompele, Elfride De Baere, and Bart Leroy. 2021. “Phenocopy of a Heterozygous Carrier of X-Linked Retinitis Pigmentosa Due to Mosaicism for a RHO Variant.” SCIENTIFIC REPORTS 11. https://doi.org/10.1038/s41598-020-80400-3.
Chicago author-date (all authors)
Strubbe, Ine, Caroline Van Cauwenbergh, Julie De Zaeytijd, Sarah De Jaegere, Marieke De Bruyne, Toon Rosseel, Stijn Van de Sompele, Elfride De Baere, and Bart Leroy. 2021. “Phenocopy of a Heterozygous Carrier of X-Linked Retinitis Pigmentosa Due to Mosaicism for a RHO Variant.” SCIENTIFIC REPORTS 11. doi:10.1038/s41598-020-80400-3.
Vancouver
1.
Strubbe I, Van Cauwenbergh C, De Zaeytijd J, De Jaegere S, De Bruyne M, Rosseel T, et al. Phenocopy of a heterozygous carrier of X-linked retinitis pigmentosa due to mosaicism for a RHO variant. SCIENTIFIC REPORTS. 2021;11.
IEEE
[1]
I. Strubbe et al., “Phenocopy of a heterozygous carrier of X-linked retinitis pigmentosa due to mosaicism for a RHO variant,” SCIENTIFIC REPORTS, vol. 11, 2021.
@article{8687534,
  abstract     = {{We describe both phenotype and pathogenesis in two male siblings with typical retinitis pigmentosa (RP) and the potentially X-linked RP (XLRP) carrier phenotype in their mother. Two affected sons, two unaffected daughters, and their mother underwent detailed ophthalmological assessments including Goldmann perimetry, color vision testing, multimodal imaging and ISCEV-standard electroretinography. Genetic testing consisted of targeted next-generation sequencing (NGS) of known XLRP genes and whole exome sequencing (WES) of known inherited retinal disease genes (RetNet-WES). Variant validation and segregation analysis were performed by Sanger sequencing. The mutational load of the RHO variant in the mother was assessed in DNA from leucocytes, buccal cells and hair follicles using targeted NGS. Both affected sons showed signs of classical RP, while the mother displayed patches of hyperautofluorescence on blue light autofluorescence imaging and regional, intraretinal, spicular pigmentation, reminiscent of a carrier phenotype of XLRP. XLRP testing was negative. RetNet-WES testing revealed RHO variant c.404G>C p.(Arg135Pro) in a mosaic state (21% of the reads) in the mother and in a heterozygous state in both sons. Targeted NGQSS of the RHO variant in different maternal tissues showed a mutation load between 25.06% and 41.72%. We report for the first time that somatic mosaicism of RHO variant c.404G>C p.(Arg135Pro) mimics the phenotype of a female carrier of XLRP, in combination with heterozygosity for the variant in the two affected sons.}},
  articleno    = {{117}},
  author       = {{Strubbe, Ine and Van Cauwenbergh, Caroline and De Zaeytijd, Julie and De Jaegere, Sarah and De Bruyne, Marieke and Rosseel, Toon and Van de Sompele, Stijn and De Baere, Elfride and Leroy, Bart}},
  issn         = {{2045-2322}},
  journal      = {{SCIENTIFIC REPORTS}},
  keywords     = {{Multidisciplinary}},
  language     = {{eng}},
  pages        = {{8}},
  title        = {{Phenocopy of a heterozygous carrier of X-linked retinitis pigmentosa due to mosaicism for a RHO variant}},
  url          = {{http://dx.doi.org/10.1038/s41598-020-80400-3}},
  volume       = {{11}},
  year         = {{2021}},
}

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