Exons 1-3 deletion in FLCN is associated with increased risk of pneumothorax in Chinese patients with Birt-Hogg-Dubé syndrome.

BACKGROUND: The pathogenic variants responsible for Birt-Hogg-Dubé syndrome (BHDS) in folliculin (FLCN) gene mostly consist of point mutations. Although large intragenic deletions/duplications have been reported in several case reports, the relationship between large intragenic deletions/duplications and phenotype in BHDS remains unclear. METHODS: We retrospectively identified and reviewed patients with a large intragenic deletion spanning exons 1-3 and analyzed their phenotypic features to compare with those of point mutation carriers in our hospital from January 1, 2017 to August 31, 2022. RESULTS: Twenty unique point mutations (including 4 novel mutations) were detected in 62 patients from 45 families (90%). Exons 1-3 deletion were identified in 8 patients from 5 families (10%) that resided in the same region, Feidong County of Anhui Province, China. Breakpoint analysis indicated that all the deletion breakpoints were flanked by Alu repeats. The prevalence of exons 1-3 deletion carriers in Feidong County was 8.1-times higher than that for BHDS in Anhui Province, suggesting a clustered phenomenon of exons 1-3 deletion. Significantly increased risk of pneumothorax was observed in those with exons 1-3 deletion compared with point mutations (91% vs. 58%, p value 0.047). The risk of renal cancer may be higher in those with exons 1-3 deletion than for those with point mutations (18% vs. 4%, p > 0.05). CONCLUSIONS: Large intragenic deletion of exons 1-3 in FLCN was identified as a local aggregation phenomenon in Feidong County, China, and was associated with a significantly higher risk of pneumothorax compared to those with point mutations.

Early mean absolute lymphocyte count in acute necrotizing pancreatitis is associated with infected pancreatic necrosis.

OBJECTIVES: Peripheral absolute lymphocyte count (ALC) has the potential to predict infected pancreatic necrosis (IPN), but requires verification. This study aimed to assess whether early mean absolute lymphocyte count is associated with the development of IPN in ANP patients using pooled data from a multicenter, randomized controlled trial and a retrospective study. METHODS: The study subjects are from the TRACE trial and a single-center cohort study. ALC during the first seven days was used to define early mean ALC. The entire cohort was then divided into quartiles of early mean ALC. Multivariable Cox proportional hazards regression (MCPHR) model was used to assess the association between early mean ALC and 90-day IPN. RESULTS: A total of 660 patients (median age, 44 years; 63.8 % males) were included and 157 (23.8 %) developed IPN within a 90-day period. The median (interquartile range, IQR) of the early mean ALC is 1.07 (0.80-1.36). All the study subjects were evenly divided into 4 groups: quartile-1 (0.33-0.79*10^9/L), quartile-2 (0.80-1.06*10^9/L), quartile-3 (1.07-1.36*10^9/L) and quartile-4 (1.37-4.01*10^9/L). The incidence of 90-day IPN was 38.3 %, 25.7 %, 19.2 % and 12.2 % for each group, respectively. In the MCPHR model, the lowest early mean ALC (quartile-1) was found to be an independent risk factor of 90-day IPN with a hazard ratio (95 %CI) of 2.21 (1.28-3.81) compared to the highest mean ALC(quartile-4) group. CONCLUSION: Among patients with ANP, early mean ALC was significantly associated with the development of IPN. Preventive strategies should be considered in patients with reduced ALC.