X‐chromosome inactivation pattern of amniocytes predicts the risk of dystrophinopathy in fetal carriers of DMD mutations

Objective To predict the risk of dystrophinopathy in fetal carriers of dystrophin gene (DMD) mutations. Methods Twenty‐three pregnant women, with a total of 25 female fetuses carrying DMD mutations, were recruited. Among them, 13 pregnant women who participated in this study were only used to analyse the incidence of induced abortion after fetuses were diagnosed as dystrophinopathy carriers. Eleven fetal carriers from 10 pregnant women were tested to analyse X‐chromosome inactivation (XCI) using amniocytes to assess the risk of dystrophinopathy. Follow‐ups were conducted on all cases. Results Approximately one‐third of fetuses were aborted before assessing the risk of dystrophinopathy. XCI analysis of amniocytes showed that 10 fetuses had random XCI patterns, and one fetus exhibited a highly skewed XCI pattern (100:0) with primary expression of the maternal X chromosome that carried the mutant allele. These 11 fetal carriers were born, and follow‐up showed that the girl who showed the skewed XCI pattern as a fetus was diagnosed with Duchenne muscular dystrophy (DMD) at the age of four. The others did not present with dystrophinopathy‐associated symptoms. Conclusions XCI was significantly implicated in symptomatic female carriers of dystrophinopathies, and XCI pattern analysis of amniocytes may be useful in predicting the risk of dystrophinopathy in fetal carriers.