Objective To study mutations in the extracellular matrix protein 1 (ECM1) gene in a family with lipoid proteinosis (LP). Methods Bi-directional DNA sequencing was used to detect the ECM1 gene in patients with LP as well as among their parents, siblings and children. Results Sequencing from the affected individuals revealed a new compound heterozygote of missense/nonsense mutations, C220G/R476X, which were not found in the control group. The father was a carrier of the missense mutation C220G and the mother was a carrier of the nonsense mutation R476X, both on one allele. The other siblings, the patients' children and their siblings' children were carriers of either C220G or R476X mutations. Conclusion A new compound heterozygous mutation of ECM1 gene was identified in this LP family.

BACKGROUND: The patients with advanced lung adenocarcinoma should select targeted drugs based on the type of tumor epidermal growth factor receptor (EGFR) gene mutation. However, it is difficult to collect tumor tissue of advanced lung adenocarcinoma, and some experts agree that peripheral blood can be used as a substitute for tumor tissue as a test specimen. This paper aimed to investigate the clinical value of ddPCR and super-amplification refractory mutation system (ARMS) in detecting EGFR gene mutation in peripheral blood of patients with advanced lung adenocarcinoma. METHODS: A total of 119 patients diagnosed in Beijing Chest Hospital Affiliated to Capital Medical University from February 2016 to February 2019 were collected, and the sensitivity and specificity of plasma ctDNA EGFR gene mutation detected by ddPCR and super-arms were compared. Some patients with positive EGFR gene mutations received oral treatment with first-line EGFR tyrosine kinase inhibitors (EGFR-TKI). The patients were divided into subgroups according to the test results. In group 1, both ddPCR and super-arms showed positive EGFR gene mutation results, with 21 cases. In group 2, ddPCR and super-arms detection of EGFR gene mutation were all negative, with 16 cases. In group 3, the ddPCR test was positive and the super-arms test was negative, with 5 cases. In group 4, the ddPCR test result was negative while the super-arms test result was positive. Since the number of patients in group 4 was 0, no statistics were included. Objective response rate (ORR) and disease control rate (DCR) were used to evaluate the short-term outcome, and progression-free survival (PFS) was compared with survival analysis to evaluate the long-term outcome. RESULTS: EGFR mutations were detected in 58 (48.7%) of 119 patients with advanced lung adenocarcinoma. The coincidence rate between ddPCR and EGFR gene mutation in tumor tissues was 82.4% (Kappa=0.647, P<0.001), the sensitivity was 74.1%, and the specificity was 90.2%. However, the coincidence degree of super-arms test and tissue test was 71.4%, the sensitivity was only 58.6%, and the specificity was 83.6%. The ORR and DCR values in group 3 were lower than those in group 1 and 2, but there was no significant difference in ORR between groups (P>0.05). Survival analysis showed that the PFS of the three groups was compared. The difference was not statistically significant (χ²=2.221, P=0.329). CONCLUSIONS ddPCR, as a high sensitivity and specificity liquid gene detection method, can be used as a reliable method to detect the mutation of plasma ctDNA EGFR gene in patients with advanced lung adenocarcinoma. The results of plasma genetic testing can also be used as the basis for predicting the efficacy of EGFR-TKIs in patients.