Novel transition c.1621C>T (p.Gln541*) in the FYCO1 gene is a major cause of congenital autosomal recessive cataract (CTRCT18) in Yakutia: results of whole exome sequencing

Congenital cataracts are a major cause of vision loss in children worldwide. Congenital autosomal recessive cataract is one of the most common orphan diseases in indigenous Yakut population (the Sakha Republic, Eastern Siberia, Russia). To identify the genetic cause of congenital cataract spread in Yakut population we performed whole exome sequencing on Illumina NextSeq 500 in one Yakut patient from family with three affected siblings, whose parents had preserved vision and revealed novel homozygous transition c.1621C>T (chr3:46009205G>A) in gene FYCO1 (3p21.31) previously known in association with congenital cataract. The c.1621C>T transition leads to premature stop-codon formation (p.Gln541*, NM_024513.3) in exon 8 of the FYCO1 gene. Variant c.1621C>T is not reported in the 1000 Genomes, the ESP6500, and the ExAC projects. Sanger sequencing confirmed the segregation of homozygosity for c.1621C>T with congenital cataract in this Yakut family: all affected siblings were homozygotes for c.1621C>T while their healthy parents were heterozygous for this variant. Subsequent screening c.1621C>T in other patients with congenital cataract allowed us to define the contribution of c.1621C>T in etiology of this disease in Yakutia. In total, 87.5% of the congenital cataract cases in Yakutia were caused by homozygous variant c.1621C>T (p.Gln541*) in the FYCO1 gene. The highest prevalence of congenital cataract caused by homozygosity for c.1621C>T was registered in the сentral districts of the Sakha Republic (Yakutia). These results suggest that the novel transition c.1621C>T (p.Gln541*) in the FYCO1 gene is a major cause of congenital autosomal recessive cataract (CTRCT18) in Yakut population in the Sakha Republic (Yakutia).

врожденная аутосомно-рецессивная катаракта, CTRCT18, ген FYCO1, якуты, популяционный изолят, Якутия, Восточная Сибирь, congenital autosomal recessive cataract, CTRCT18, FYCO1, Yakuts, population isolate, Sakha Republic, Eastern Siberia

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