OBJECTIVE: To explore the genetic basis of a Chinese pedigree affected with Dyggve-Melchior-Clausen syndrome. METHODS: Whole exome sequencing and Sanger sequencing were carried out to detect potential pathogenic variants associated with the syndrome. The function of candidate variant was verified by Western blotting. RESULTS: A novel homozygous variant, c.1222delG of the DYM gene was detected in the two affected siblings, for which both parents were heterozygous carriers. The variant has caused replacement of Asp by Met at amino acid 408 and generate a premature stop codon p.Asp408Metfs*10. Western blotting confirmed that the variant can result in degradation of the mutant DYM protein, suggesting that it is a loss of function variant. CONCLUSION The homozygous c.1222delG frameshift variant of the DYM probably underlay the Dyggve-Melchior-Clausen syndrome in the two affected siblings. Above findings has enabled clinical diagnosis and genetic counseling for the family.
China ; Dwarfism/genetics* ; Humans ; Intellectual Disability ; Osteochondrodysplasias/genetics* ; Pedigree

Objective:To explore the diagnostic process and outcomes of patients with aplastic anemia (AA) who received outpatient treatment in a real-world setting.Methods:The diagnostic processes, treatment regimens, and outcomes of 176 patients with AA treated in outpatient centers from January 2018 to December 2019 were reviewed.Results:The median interval from the onset of symptoms to the first visit was 7 (5-120) months. Complaints during the first visit included bleeding (52.3% ) , anemia (51.7% ) , and infection (6.8% ) . For diagnosis, 168 patients (95.5% ) underwent bone marrow aspiration; however, only 22 of them (17.1% ) consented aspiration in multiple sites (sternum) . The completion rate of bone marrow biopsy was 85.1% (143/168) ; flow immunophenotype and karyotype analyses were performed on 59.5% (100/168) and 58.9% (99/168) of AA patients, respectively, and the culture of clonal forming units by bone marrow mononuclear cells was performed on 26.8% (45/168) of AA patients. The most preferred regimen was cyclosporine combined with androgen and levamisole (43.8% , 77 patients) , followed by cyclosporine combined with androgen (25.6% , 45 patients) . Cyclosporine alone was administered in 24 patients (13.6% ) and androgen alone in 16 patients (9.1% ) . Furthermore, 14 patients (7.9% ) did not consent to any drugs or only chose traditional Chinese medicine. The patients were divided according to the frequencies of follow-up: regular follow-up group (≥4 times/year, n=130) and irregular group (<4 times/year, n=46) . The former had a higher 6-month remission rate (52.5% vs 28.0% , P=0.005) , a greater high-quality remission rate in 12 months (40.7% vs 16.7% , P=0.027) , and a lower relapse rate in 24 months (4.4% vs 36.4% , P=0.001) . Conclusion:In real-world settings, bone marrow aspiration in multiple sites should be addressed in outpatient treatment for AA diagnostic work-up, including PNH clone screening, flow immunophenotype, chromosome karyotype analysis, and culture of clonal forming units. Patients with AA who follow regular visits were more likely to achieve high-quality remission and a lower relapse rate. Visits at least four times per year are recommended for AA patients undergoing outpatient treatment.