Shared Founder Effect of the LIPH Variant Underlies the High Prevalence of Autosomal Recessive Woolly Hair/Hypotrichosis in Korea and Japan.

PURPOSE: Autosomal Recessive Woolly Hair/Hypotrichosis (ARWH) due to LIPH variants is common in East Asia, especially in Japan, but its genetic architecture in the Korean population and the ancestral origin of these variants remain uncharacterized. This study aimed to define the molecular spectrum of LIPH variants in a Korean cohort and trace the history of East Asian founder variants. METHODS: We analyzed pathogenic variant frequencies from public genomic databases and performed exome sequencing and haplotype analysis on 32 Korean ARWH participants from independent families. RESULTS: The p.Cys246Ser founder variant was highly prevalent in both Korea and Japan. Haplotype analysis confirmed an identical ancestral origin, providing strong evidence for a shared founder effect between Korea and Japan. This shared genetic history is the primary driver for the high prevalence of ARWH, estimated at 1 in 7,092 in Korea and 1 in 4,975 in Japan. Furthermore, we identified p.Asp207His as a newly identified, Korean-specific founder variant. CONCLUSION: The high prevalence of LIPH-associated ARWH in East Asia is explained by a shared founder effect of the p.Cys246Ser variant between Korea and Japan, revealing a significant public health burden. The discovery of an unreported Korean founder variant further refines the population-specific genetic history of this disorder.