Content » Vol 100, October

Investigative Report

Massively Parallel Sequencingof the Filaggrin Gene Reveals an Association Between FLG Loss-of-function Mutations and Leprosy

Wenhao Shi, Zihao Mi, Zhenzhen Wang, Huimin Zhang, Na Wang, Zhe Wang, Bowen Zhang, Qianqian Xia, Yueqian Yu, Gongqi Yu, Lele Sun, Xian Fu, Chuan Wang, Hong Liu, Furen Zhang
DOI: 10.2340/00015555-3663


Filaggrin, encoded by the FLG gene, plays a crucial role in the barrier function of epidermis, but the association between FLG loss-of-function mutations and infectious skin diseases has not been systematically studied. FLG coding sequences from 945 patients with leprosy and 916 healthy controls were captured and enriched using an array-based high-throughput system, and subjected to next-generation sequencing. The loss-of-function mutations found were further validated by Sanger sequencing. A total of 21 loss-of-function mutations were found in 945 patients with leprosy, with a carrier rate of 17.53%, while the prevalence of these mutations in 916 healthy controls was 14.77%, which was significantly lower than in patients. Two individual FLG loss-of-function mutations (K4022X and Q1790X) were found to be significantly associated with leprosy. These results suggest a possible role for filaggrin in defending against leprosy pathogens.


Leprosy is a chronic infectious skin disease caused by the pathogen Mycobacterium leprae, which shows strong genetic predisposition. This study sequenced the FLG gene coding sequence in a large cohort of patients with leprosy and matched healthy controls. The results show that the carrier rate of FLG loss-of-function mutations in patients with leprosy was significantly higher than that in healthy controls. Skin barrier deficiency, caused by FLG loss-of-function mutations, may contribute to the pathogenesis of leprosy by increasing the risk of infection through impaired skin. These results suggest a possible role for filaggrin in defending against leprosy pathogens.

Supplementary content


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