Carrier Frequency and Prevalence of Citrin Deficiency in East Asians and Koreans Based on Comprehensive Analysis of Pathogenic Variants.

BACKGROUND

: Citrin deficiency is an autosomal recessive disorder caused by pathogenic variants in , presenting with various age-dependent clinical phenotypes and a broad spectrum of severity. However, few studies have examined the frequency and prevalence of citrin deficiency. We aimed to analyze the carrier frequency and disease prevalence in East Asian populations and Koreans.

METHODS

: We comprehensively reviewed the literature and conducted a cross-sectional study to analyze genomic databases, including the Genome Aggregation Database (gnomAD), Korean Variant Archive (KOVA), and Tohoku Medical Megabank Organization (ToMMo), to identify pathogenic variants in East Asian populations. A founder 3-kilobase (kb) insertion in intron 16 of was investigated using whole-genome sequencing data from 681 Koreans with the Linux grep command.

RESULTS

: Twenty-three pathogenic variants were identified, with c.852_855del being the most common. Analysis of data from 17,501 East Asian individuals in the gnomAD and ToMMo databases revealed a carrier frequency of 1 in 62 people. Analysis of data from 7,214 individuals in the gnomAD and KOVA databases revealed a carrier frequency of 1 in 86, corresponding to an estimated disease prevalence of 1 in 29,502. c.1177+1G>A was identified as the most prevalent pathogenic variant in Koreans. The 3 kb insertion in intron 16 was detected in three out of 681 individuals, indicating a carrier frequency of 1 in 228.

CONCLUSIONS

: The high carrier frequency of citrin deficiency in East Asians highlights the need for enhanced genetic screening and counseling, particularly in Korea, providing a valuable reference for future studies on genetic diversity and pathogenic variants in this population.