Characteristics of Dystrophin Gene Mutations Among Chinese Patients as Revealed by Multiplex Ligation–Dependent Probe Amplification

Abstract

To verify whether dystrophin gene mutations among Chinese patients feature different types and frequencies from other populations. Multiplex ligation-dependent probe amplification (MLPA) in combination with multiplex PCR (mPCR) and/or short tandem repeat (STR)-based linkage analysis were applied in a large series of Chinese families affected with Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy (BMD). There were a total of 19 cases seeking prenatal diagnosis during their second pregnancies. Of the 59 family trios (51 with DMD and 8 with BMD), 40 were found to have carried various mutations of the dystrophin gene. In addition to deletions and duplications within the mutational hotspots identified by both methods, 10 mutations missed by mPCR were detected by MLPA, among which at least 3 were of rare types. Combined MLPA and linkage analysis also achieved prenatal diagnoses in all of the 19 amniocentesis samples. Mutations of dystrophin gene among Chinese patients showed a diverse spectrum, with similarity to as well as discrepancies from other populations. For the comprehensive coverage of all exons of the dystrophin gene, MLPA should be the method of choice for initial screening of DMD/BMD patients. When combined with STR-based analysis, it can achieve diagnosis in as much as 70-80% of all referred cases.