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

• Published in: European Journal of Human Genetics
• Main Authors: Barashkov, Nikolay A., Konovalov, Fedor A., Borisova, Tuyara V., Teryutin, Fedor M., Solovyev, Aisen V., Pshennikova, Vera G., Sapojnikova, Nadejda V., Vychuzhina, Lyubov S., Romanov, Georgii P., Gotovtsev, Nyurgun N., Morozov, Igor V., Bondar, Alexander A., Platonov, Fedor A., Burtseva, Tatiana E., Khusnutdinova, Elza K., Posukh, Olga L., Fedorova, Sardana A.
• Format: Text
• Language: English
• Published: Springer International Publishing 2021
• Subjects: Article; Chukchi; Evenks; Yakut; Yakuts; Siberia
• Online Access: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187664/; http://www.ncbi.nlm.nih.gov/pubmed/33767456; https://doi.org/10.1038/s41431-021-00833-w

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.