Outstanding Characteristics of Birt–Hogg–Dube Syndrome in Korea

Abstract

Birt–Hogg–Dube (BHD) is a rare genetic disorder characterized by multiple lung cysts, typical skin manifestations, and renal tumors. We prospectively enrolled thirty-one subjects from four South Korean institutions with typical lung cysts, and next-generation sequencing was conducted. We prospectively enrolled thirty-one subjects from four Korean institutions with typical lung cysts. Next-generation sequencing was performed to investigate mutations in the following genes: FLCN, TSC1, TSC2, CFTR, EFEMP2, ELN, FBLN5, LTBP4, and SERPINA1. BHD was diagnosed in 11 of the 31 enrolled subjects (35.5%; FLCN mutations). Notably, we identified three novel mutations (c.1098G>A, c.139G>T, and c.1335del) that have not been previously reported. In addition to FLCN mutations, we also observed mutations in CFTR (16.1%), LTBP4 (9.7%), TSC2 (9.7%), TSC1 (3.2%), ELN (3.2%), and SERPINA1 (3.2%). According to a systematic review of 45 South Korean patients with BHD, the prevalence of pneumothorax (72.7%) was greater in South Korea than in the rest of the world (50.9%; p = 0.003). The prevalence of skin manifestations (13.6%) and renal tumors (9.1%) was lower in Korea than in the rest of the world, at 47.9% [p < 0.001] and 22.5% [p = 0.027], respectively). This study confirmed a significant prediction model for BHD based on age, number of lung cysts (>40), and maximal diameter of lung cysts (>2 cm) regardless of skin manifestations and renal tumors. Importantly, three novel mutations (c.1098G>A, c.139G>T, and c.1335del) were identified. In conclusion, South Korean patients with BHD display characteristics that are different from those observed in patients of other nationalities. Detailed characterization of lung cysts is needed to define BHD, especially in South Korea, even if patients do not present with skin or renal lesions.

Genetic and Clinical Profiling of Korean Patients with Birt–Hogg–Dubé Syndrome

“…This study investigated nine Korean patients with BHDS, with a mean diagnosis age of 49.2±18.2 years, consistent with previous Korean studies [5,9]. The rates of pulmonary cysts (86%), renal cancer (22%), and skin lesions (38%) were similar to those reported in earlier studies on Korean patients with BHDS [9,18].…”

Amelioration of Fibrosis via S1P Inhibition Is Regulated by Inactivation of TGF-β and SPL Pathways in the Human Cornea

“…One group demonstrated the compensation of LTBP4 for the loss of LTBP2 in the microfibril formation of mouse embryonic fibroblasts [ 82 ]. Furthermore, LTBP4 genetic mutations have been linked to various disorders, including cutis laxa [ 81 , 83 , 84 , 85 ], scleroderma [ 81 , 86 ], pulmonary [ 81 , 87 , 88 , 89 ], cardiac [ 81 , 90 , 91 , 92 ], and cancer [ 81 , 93 , 94 ]. Our group reported that both TGF-β1 and TGF-β3 modulated LTBP1 expression, but only TGF-β3 modulated LTBP2 expression in 3D HCF constructs.…”