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Barashkov NA, Konovalov FA, Borisova TV, et al. Autosomal recessive cataract (CTRCT18) in the Yakut population isolate of Eastern Siberia: a novel founder variant in the FYCO1 gene. Eur J Hum Genet. 2021;29(6):965-976doi: 10.1038/s41431-021-00833-w.
Barashkov, N. A., Konovalov, F. A., Borisova, T. V., Teryutin, F. M., Solovyev, A. V., Pshennikova, V. G., Sapojnikova, N. V., Vychuzhina, L. S., Romanov, G. P., Gotovtsev, N. N., Morozov, I. V., Bondar, A. A., Platonov, F. A., Burtseva, T. E., Khusnutdinova, E. K., Posukh, O. L., & Fedorova, S. A. (2021). Autosomal recessive cataract (CTRCT18) in the Yakut population isolate of Eastern Siberia: a novel founder variant in the FYCO1 gene. European journal of human genetics : EJHG, 29(6), 965-976. https://doi.org/10.1038/s41431-021-00833-w
Barashkov, Nikolay A, et al. "Autosomal recessive cataract (CTRCT18) in the Yakut population isolate of Eastern Siberia: a novel founder variant in the FYCO1 gene." European journal of human genetics : EJHG vol. 29,6 (2021): 965-976. doi: https://doi.org/10.1038/s41431-021-00833-w
Barashkov NA, Konovalov FA, Borisova TV, Teryutin FM, Solovyev AV, Pshennikova VG, Sapojnikova NV, Vychuzhina LS, Romanov GP, Gotovtsev NN, Morozov IV, Bondar AA, Platonov FA, Burtseva TE, Khusnutdinova EK, Posukh OL, Fedorova SA. Autosomal recessive cataract (CTRCT18) in the Yakut population isolate of Eastern Siberia: a novel founder variant in the FYCO1 gene. Eur J Hum Genet. 2021 Jun;29(6):965-976. doi: 10.1038/s41431-021-00833-w. Epub 2021 Mar 25. PMID: 33767456; PMCID: PMC8187664.
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Eur J Hum Genet. 2021 Jun;29(6):965-976. doi: 10.1038/s41431-021-00833-w. Epub 2021 Mar 25.

Autosomal recessive cataract (CTRCT18) in the Yakut population isolate of Eastern Siberia: a novel founder variant in the FYCO1 gene.

European journal of human genetics : EJHG

Nikolay A Barashkov, Fedor A Konovalov, Tuyara V Borisova, Fedor M Teryutin, Aisen V Solovyev, Vera G Pshennikova, Nadejda V Sapojnikova, Lyubov S Vychuzhina, Georgii P Romanov, Nyurgun N Gotovtsev, Igor V Morozov, Alexander A Bondar, Fedor A Platonov, Tatiana E Burtseva, Elza K Khusnutdinova, Olga L Posukh, Sardana A Fedorova

Affiliations

  1. Laboratory of Molecular Genetics, Yakut Science Centre of Complex Medical Problems, Yakutsk, Russian Federation. [email protected].
  2. Laboratory of Molecular Biology, M.K. Ammosov North-Eastern Federal University, Yakutsk, Russian Federation. [email protected].
  3. Genomed Ltd, Moscow, Russian Federation.
  4. Laboratory of Molecular Biology, M.K. Ammosov North-Eastern Federal University, Yakutsk, Russian Federation.
  5. Laboratory of Molecular Genetics, Yakut Science Centre of Complex Medical Problems, Yakutsk, Russian Federation.
  6. Department of Ophthalmology, Republican Hospital #1 - National Centre of Medicine, Yakutsk, Russian Federation.
  7. SB RAS Genomics Core Facility, Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russian Federation.
  8. Novosibirsk State University, Novosibirsk, Russian Federation.
  9. Medical Institute, M.K. Ammosov North-Eastern Federal University, Yakutsk, Russian Federation.
  10. Laboratory of the Children Health Monitoring and Medical-environmental Research, Yakut Science Centre of Complex Medical Problems, Yakutsk, Russian Federation.
  11. Laboratory of Human Molecular Genetics, Institute of Biochemistry and Genetics, Ufa Federal Research Center of Russian Academy of Sciences, Ufa, Russian Federation.
  12. Department of Genetics and Fundamental Medicine, Bashkir State University, Ufa, Russian Federation.
  13. Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russian Federation.

PMID: 33767456 PMCID: PMC8187664 DOI: 10.1038/s41431-021-00833-w

Abstract

Congenital autosomal recessive cataract with unknown genetic etiology is one of the most common Mendelian diseases among the Turkic-speaking Yakut population (Eastern Siberia, Russia). To identify the genetic cause of congenital cataract spread in this population, we performed whole-exome sequencing (Illumina NextSeq 500) in one Yakut family with three affected siblings whose parents had preserved vision. We have revealed the novel homozygous c.1621C>T transition leading to premature stop codon p.(Gln541*) in exon 8 of the FYCO1 gene (NM_024513.4). Subsequent screening of c.1621C>T p.(Gln541*) revealed this variant in a homozygous state in 25 out of 29 Yakut families with congenital cataract (86%). Among 424 healthy individuals from seven populations of Eastern Siberia (Russians, Yakuts, Evenks, Evens, Dolgans, Chukchi, and Yukaghirs), the highest carrier frequency of c.1621C>T p.(Gln541*) was found in the Yakut population (7.9%). DNA samples of 25 homozygous for c.1621C>T p.(Gln541*) patients with congenital cataract and 114 unaffected unrelated individuals without this variant were used for a haplotype analysis based on the genotyping of six STR markers (D3S3512, D3S3685, D3S3582, D3S3561, D3S1289, and D3S3698). The structure of the identified haplotypes indicates a common origin for all of the studied mutant chromosomes bearing c.1621C>T p.(Gln541*). The age of the с.1621C>T p.(Gln541*) founder haplotype was estimated to be approximately 260 ± 65 years (10 generations). These findings characterize Eastern Siberia as the region of the world with the most extensive accumulation of the unique variant c.1621C>T p.(Gln541*) in the FYCO1 gene as a result of the founder effect.

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