Genotypes and Phenotypes of Small Mutations in Chinese Patients With Dystrophinopathies.

Dystrophinopathies are a group of neuromuscular disorders resulting from mutations in , including Duchenne muscular dystrophy (DMD), intermediate muscular dystrophy (IMD), and Becker muscular dystrophy (BMD). Herein, we present the characteristics of small mutations in Chinese patients with dystrophinopathies, and explore genotype-phenotype correlations. In our cohort, 115 patients with small mutations (18.49% of all patients) were included and mutations were detected by either Sanger (53.91%) or next generation sequencing (46.09%). In total, 106 small mutations were detected, 28 of which (26.42%) had not been reported previously. The most common mutations were nonsense mutations (52.17%), followed by splicing (24.35%), frameshift (17.39%), and missense mutations (5.22%), in addition to a single untranslated region mutation (0.87%). We discovered distinct mutation characteristics in our patients, such as different positional distributions, indicating different exon skipping therapy strategies for small mutations in Chinese patients. Almost all patients (96.51%) with truncating or missense mutations, were covered by triple/double/single-exon skipping therapy; the most frequent single-exon skipping strategy was skipping exon 32, applicable for 8.51% of patients. Furthermore, splicing classification grades were correlated with phenotypes in nonsense mutations ( < 0.001), and serum creatinine levels differed significantly between DMD/IMD and BMD for patients ≤ 16 years old ( = 0.002). These observations can further aid prognostic judgment and guide treatment. In conclusion, the mutation characteristics and genotype-phenotype correlations in Chinese patients with dystrophinopathies and small mutations could provide insights into the molecular mechanisms of pathogenesis, diagnosis, and treatment designs.