Sisters of probands with confirmed DMD dystrophin gene mutations. Including mothers, maternal grandmothers, maternal aunts and
Patients (proband), symptomatic females and their relatives, The study participants were selected between JanuaryĢ013 and October 2017 at the First Affiliated Hospital of Guangxi Method for the detection of deletions/duplications and small Screening for MCs of DMD/BMD, and describes an effective, accurate The present study presents a non-invasive, easy The status of probable carriers wasĭetermined by MLPA and Sanger sequencing according to the mutations Panel based on next-generation sequencing (NGS), was applied toĭetect the MCs. Multiplex ligation-dependent probe amplification (MLPA)įor exons of the dystrophin gene, combined with a muscle disease Transaminase (ALT) and aspartate transaminase (AST) levels wereĪnalyzed. (CK) level of the subjects, and its correlation with alanine In the present study, clinical data were collectedĪnd analyzed from 154 probable female carriers. Required for diagnosis, particularly for genetic consulting and Genetic analysis of the dystrophin gene is typically Identification of DMD/BMD carriers may presentĬhallenges, particularly in the absence of a family history ofĭMD/BMD. Diagnosis of DMD/BMD carriers is based onĬlinical symptoms, family history, biochemistry markers,Įchocardiography, pathology, molecular genetic analysis and Patients even have rapidly progressive muscular dystrophy similar Muscle weakness to severe abnormal gait with frequent falls, andĭifficulty in rising from the floor or walking on tiptoes. The most important hotspots are located in exonĭMD and BMD are X-linked recessive diseases, and thus females areĪsymptomatic, while only 2.5–10% of carriers are symptomatic andĬlassified as manifesting carriers (MCs) ( 5). Approximately 60–65% of mutations areĭeletions, 5–15% are duplications and 30% are point mutationsĭystrophin gene. Live male births and 1 case per 6,000–8,000 live male births, Occur with a birth prevalence rate of 15.9–19.5 cases per 100,000 Which encodes dystrophin protein at the Xp-21 locus. Muscular dystrophy (BMD) are the most common childhood muscularĭystrophies, and are caused by mutations in the dystrophin gene, The ROC curve analysis also demonstrated that CK level was an excellent predictor for distinguishing DMD/BMD carriers.ĭuchenne muscular dystrophy (DMD) and Becker MLPA for exons of the dystrophin gene, along with NGS and Sanger sequencing, was effective for the diagnosis of MCs and for determining the status of probable carriers.
In addition, DMD was positively correlated with the CK, alanine transaminase and aspartate transaminase levels of the carriers. The area under the receiver operating characteristic (ROC) curve of creatine kinase (CK) was 0.822, with a sensitivity of 65.38% and specificity of 92.1%. Among the 74 asymptomatic carriers, 41.89% harbored deletion mutations, including 2 cases with suspected germline mosaicism and no mutation in the dystrophin gene, while 44.59% harbored point mutations in exons and only 10 cases (13.51%) carried duplication mutations. The 4 MCs exhibited duplication mutations.
A total of 154 female were enrolled, among which 78 cases were found to be carriers, including 4 MCs and 74 asymptomatic female carriers. In addition, the status of probable carriers was determined by MLPA or Sanger sequencing, according to the mutations of probands. MCs underwent multiplex ligation‑dependent probe amplification (MLPA) for dystrophin gene exons combined with muscle disease panel test based on a next‑generation sequencing (NGS) platform. Clinical data from probable carriers and MCs were collected and analyzed. The present study aimed to determine the genetic status of manifesting carriers (MCs) of Duchenne muscular dystrophy (DMD)/Becker muscular dystrophy (BMD) and asymptomatic carriers with a family history of DMD/BMD, and identify potential simple and reliable methods for screening dystrophinopathy carriers.