Cornea Arcus and Dyslipidemia in Unrelated Adults With Monoallelic Germline Variants in the <i>Glucokinase Regulator</i> Gene

Variants in the <i>Glucokinase Regulator</i> (<i>GCKR</i>) gene are increasingly being detected with growing applications of genomic sequencing technologies. Despite the crucial roles of the <i>GCKR</i> gene in energy homeostasis, the clinical applications of <i>GCKR</i> variants are currently limited. We observed that a large proportion of <i>GCKR</i> variants that are available in gnomAD database (https://gnomad.broadinstitute.org/) lacked adequate evidence of pathogenicity or benign impact. We highlight the clinical need for an improved understanding of <i>GCKR</i> variants by presenting 2 compelling cases of unrelated families (3 individuals in total) who harbor rare <i>GCKR</i> variants in the context of cornea arcus and hyperlipidemia. Our observations underscore the burgeoning need for functional as well as family segregation studies to facilitate the clinical applications of <i>GCKR</i> variants.