Dynamic monitoring of UBA1 somatic mutations in patients with relapsing polychondritis

• Published in: Orphanet journal of rare diseases Vol. 19; no. 1; p. 1
• Main Authors: Duan, Suying, Luo, Haiyang, Wang, Yunchao, Jiang, Dongbin, Liu, Jiajia, Li, Jiaqi, Zheng, Honglin, Zhao, Taiqi, Liu, Chenyang, Zhang, Hang, Mao, Chengyuan, Zhang, Lei, Xu, Yuming
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 02.01.2024; BioMed Central; BMC
• Subjects: Alleles; Analysis; Anemia; Asian People; Connective tissue diseases; Development and progression; Disease; Diseases; DNA sequencing; Droplet digital PCR; Dynamic monitoring; Enzymes; Genetic aspects; Health aspects; Humans; Inflammatory diseases; Leukemia; Male; Medical research; Medicine, Experimental; Mutation; Mutation - genetics; Nucleotide sequencing; Patients; Peripheral blood; Polychondritis; Polychondritis, Relapsing - genetics; Rare diseases; Relapse; Relapsing polychondritis; Skin; Somatic mutations; UBA1; Ubiquitin-Activating Enzymes - genetics; Vacuoles; VEXAS; China; Droplet digital PCR; UBA1; Somatic mutations; Dynamic monitoring; Relapsing polychondritis; VEXAS
• ISSN: 1750-1172; 1750-1172
• DOI: 10.1186/s13023-023-03003-x

Commonly clinically diagnosed with relapsing polychondritis (RP), vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome (VEXAS) is a recently identified autoinflammatory disease caused by UBA1 somatic mutations. The low frequency and dynamic changes challenge the accurate detection of somatic mutations. The present study monitored these mutations in Chinese patients with RP. We included 44 patients with RP. Sanger sequencing of UBA1 was performed using genomic DNA from peripheral blood. Droplet digital polymerase chain reaction (ddPCR) was performed to screen low-prevalence somatic variants. Multiple ddPCR detections were performed using available blood samples collected at different follow-up time points. Three male patients were UBA1 somatic mutation carriers. Sanger sequencing detected the somatic UBA1 variant c.122T > C (p.Met41Thr) in two male patients. Initial ddPCR confirmed the variant in the two patients, with allele fractions of 73.75% and 88.46%, respectively, while yielding negative results in other patients. Subsequent ddPCR detected the somatic variant (c.122T > C) with low prevalence (1.02%) in another male patient from blood samples collected at a different time point, and confirmed dynamically fractional abundance in one patient with VEXAS, with allele fractions of 73.75%, 61.28%, 65.01%, and 73.75%. Nine patients assessed by ddPCR at different time points remained negative. We report UBA1 variants in patients with RP in the Chinese population for the first time. Multiple ddPCR detections from samples collected at different time points can enhance sensitivity and should be considered for patients with initial negative ddPCR results.