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A nonsense mutation in FAM161A is a recurrent founder allele in Dutch and Belgian individuals with autosomal recessive retinitis pigmentosa

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Abstract
PURPOSE. To identify mutations in FAM161A underlying autosomal recessive retinitis pigmentosa (arRP) in the Dutch and Belgian populations and to investigate whether common FAM161A-associated phenotypic features could be identified. METHODS. Homozygosity mapping, amplification-refractory mutation system (ARMS) analysis, and Sanger sequencing were performed to identify mutations in FAM161A. Microsatellite and SNP markers were genotyped for haplotype analysis. Patients with biallelic mutations underwent detailed ophthalmologic examinations, including measuring best-corrected visual acuity, extensive fundus photography with reflectance and autofluorescence imaging, and optical coherence tomography. RESULTS. Homozygosity mapping in 230 Dutch individuals with suspected arRP yielded five individuals with a homozygous region harboring FAM161A. Sanger sequencing revealed a homozygous nonsense mutation (c.1309A>T; p.[Arg437*]) in one individual. Subsequent ARMS analysis and Sanger sequencing in Dutch and Belgian arRP patients resulted in the identification of seven additional individuals carrying the p.(Arg437*) mutation, either homozygously or compound heterozygously with another mutation. Haplotype analysis identified a shared haplotype block of 409 kb surrounding the p.(Arg437*) mutation in all patients, suggesting a founder effect. Although the age of onset was variable among patients, all eight developed pronounced outer retinal loss with severe visual field defects and a bull's eye-like maculopathy, followed by loss of central vision within 2 decades after the initial diagnosis in five subjects. CONCLUSIONS. A founder mutation in FAM161A p.(Arg437*) underlies approximately 2% of arRP cases in the Dutch and Belgian populations. The age of onset of the retinal dystrophy appears variable, but progression can be steep, with almost complete loss of central vision later in life.
Keywords
retinitis pigmentosa, FAM161A, founder mutation, bull's eye-like maculopathy, TIME QUANTITATIVE PCR, REVEALS, CILIOPATHIES, DISRUPTION, COMPONENT, COMPLEX

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MLA
Van Schil, Kristof et al. “A Nonsense Mutation in FAM161A Is a Recurrent Founder Allele in Dutch and Belgian Individuals with Autosomal Recessive Retinitis Pigmentosa.” INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE 56.12 (2015): 7418–7426. Print.
APA
Van Schil, K., Klevering, B. J., Leroy, B., Pott, J. W. R., Bandah-Rozenfeld, D., Zonneveld-Vrieling, M. N., Sharon, D., et al. (2015). A nonsense mutation in FAM161A is a recurrent founder allele in Dutch and Belgian individuals with autosomal recessive retinitis pigmentosa. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 56(12), 7418–7426.
Chicago author-date
Van Schil, Kristof, B Jeroen Klevering, Bart Leroy, Jan Willem R Pott, Dikla Bandah-Rozenfeld, Marijke N Zonneveld-Vrieling, Dror Sharon, et al. 2015. “A Nonsense Mutation in FAM161A Is a Recurrent Founder Allele in Dutch and Belgian Individuals with Autosomal Recessive Retinitis Pigmentosa.” Investigative Ophthalmology & Visual Science 56 (12): 7418–7426.
Chicago author-date (all authors)
Van Schil, Kristof, B Jeroen Klevering, Bart Leroy, Jan Willem R Pott, Dikla Bandah-Rozenfeld, Marijke N Zonneveld-Vrieling, Dror Sharon, Anneke I den Hollander, Frans PM Cremers, Elfride De Baere, Rob W Collin, and L Ingeborgh van den Born. 2015. “A Nonsense Mutation in FAM161A Is a Recurrent Founder Allele in Dutch and Belgian Individuals with Autosomal Recessive Retinitis Pigmentosa.” Investigative Ophthalmology & Visual Science 56 (12): 7418–7426.
Vancouver
1.
Van Schil K, Klevering BJ, Leroy B, Pott JWR, Bandah-Rozenfeld D, Zonneveld-Vrieling MN, et al. A nonsense mutation in FAM161A is a recurrent founder allele in Dutch and Belgian individuals with autosomal recessive retinitis pigmentosa. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE. 2015;56(12):7418–26.
IEEE
[1]
K. Van Schil et al., “A nonsense mutation in FAM161A is a recurrent founder allele in Dutch and Belgian individuals with autosomal recessive retinitis pigmentosa,” INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, vol. 56, no. 12, pp. 7418–7426, 2015.
@article{7178498,
  abstract     = {{PURPOSE. To identify mutations in FAM161A underlying autosomal recessive retinitis pigmentosa (arRP) in the Dutch and Belgian populations and to investigate whether common FAM161A-associated phenotypic features could be identified. 
METHODS. Homozygosity mapping, amplification-refractory mutation system (ARMS) analysis, and Sanger sequencing were performed to identify mutations in FAM161A. Microsatellite and SNP markers were genotyped for haplotype analysis. Patients with biallelic mutations underwent detailed ophthalmologic examinations, including measuring best-corrected visual acuity, extensive fundus photography with reflectance and autofluorescence imaging, and optical coherence tomography. 
RESULTS. Homozygosity mapping in 230 Dutch individuals with suspected arRP yielded five individuals with a homozygous region harboring FAM161A. Sanger sequencing revealed a homozygous nonsense mutation (c.1309A>T; p.[Arg437*]) in one individual. Subsequent ARMS analysis and Sanger sequencing in Dutch and Belgian arRP patients resulted in the identification of seven additional individuals carrying the p.(Arg437*) mutation, either homozygously or compound heterozygously with another mutation. Haplotype analysis identified a shared haplotype block of 409 kb surrounding the p.(Arg437*) mutation in all patients, suggesting a founder effect. Although the age of onset was variable among patients, all eight developed pronounced outer retinal loss with severe visual field defects and a bull's eye-like maculopathy, followed by loss of central vision within 2 decades after the initial diagnosis in five subjects. 
CONCLUSIONS. A founder mutation in FAM161A p.(Arg437*) underlies approximately 2% of arRP cases in the Dutch and Belgian populations. The age of onset of the retinal dystrophy appears variable, but progression can be steep, with almost complete loss of central vision later in life.}},
  author       = {{Van Schil, Kristof and Klevering, B Jeroen and Leroy, Bart and Pott, Jan Willem R and Bandah-Rozenfeld, Dikla and Zonneveld-Vrieling, Marijke N and Sharon, Dror and den Hollander, Anneke I and Cremers, Frans PM and De Baere, Elfride and Collin, Rob W and van den Born, L Ingeborgh}},
  issn         = {{0146-0404}},
  journal      = {{INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE}},
  keywords     = {{retinitis pigmentosa,FAM161A,founder mutation,bull's eye-like maculopathy,TIME QUANTITATIVE PCR,REVEALS,CILIOPATHIES,DISRUPTION,COMPONENT,COMPLEX}},
  language     = {{eng}},
  number       = {{12}},
  pages        = {{7418--7426}},
  title        = {{A nonsense mutation in FAM161A is a recurrent founder allele in Dutch and Belgian individuals with autosomal recessive retinitis pigmentosa}},
  url          = {{http://dx.doi.org/10.1167/iovs.15-17920}},
  volume       = {{56}},
  year         = {{2015}},
}

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