Abstract: Objective To explore the clinical phenotypes and gene variation characteristics of a female child with Duchenne muscular dystrophy, and to explore its molecular genetic pathogenesis. Methods Clinical data and muscle biopsy of the child were analyzed. Multiplex ligation-dependent probe amplification(MLPA)and Ion Torrent amplicon sequencing were performed to detect variants in the DMD gene of the child and her parents. Karyotype analysis and array-based comparative genomic hybridization(a-CGH)were carried out for the detection of chromosome variations. In addition, human androgen receptor gene methylation-specific PCR(HUMARA-MSP)was conducted to identify the X chromosome inactivation skewing. Results The patient was three years old at the first visit. The main clinical symptoms were increased creatine kinase(CK)level and reduced athletic capacity. Muscle pathology showed myodystrophic changes and loss of dystrophin protein. MLPA did not detect deletion and duplication mutations in the DMD gene. Ion Torrent amplicon sequencing revealed heterozygous c.10223 + 1G>A in the DMD gene, a spontaneous mutation. Chromosome karyotypes were normal, and a-CGH did not detect chromosomal abnormalities. Significant X chromosome inactivation skewing in this patient was confirmed by HUMARA-MSP. Conclusion The child carried a heterozygous c.10223+1G>A in the DMD gene, and the X chromosome inactivation skewing was the cause of DMD.

Key words: Duchenne muscular dystrophy, X chromosome inactivation, Human androgen-receptor gene methylation-specific PCR, Female