Molecular genetic testing and diagnosis strategies for dystrophinopathies in the era of next generation sequencing

Publication date: Available online 17 January 2019Source: Clinica Chimica ActaAuthor(s): Kuo Zhang, Xin Yang, Guigao Lin, Yanxi Han, Jinming LiAbstractDuchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X-linked recessive, inherited neuromuscular disorders, caused by pathogenic variants in the dystrophin gene that encodes the dystrophin protein. A number of mutations have been identified in the past years, producing dystrophin diversity and resulting in mild to severe phenotypes in patients. Mutations in the dystrophin gene can be characterized by laboratory testing to confirm a clinical diagnosis of DMD/BMD. Traditional genetic diagnostic strategy for DMD/BMD involves the initial detection of large mutations, followed by the detection of smaller mutations, where two or more analytical methods are employed. With the development of next generation sequencing (NGS) technology, comprehensive mutational screening for all variant types can be performed on a single platform in patients and carriers, although further optimization and validation are required. Furthermore, the discovery of cell-free fetal DNA (cffDNA) in maternal plasma provides basis for noninvasive prenatal diagnosis of DMD/BMD. Here, we discuss the correlation between genotype and phenotype, the current methods of molecular genetic testing and genetic diagnostic strategy for probands and female carriers of DMD/BMD, the diagnostic ability of a comprehensive targeted NGS strategy and the possibi...

Source: Clinica Chimica Acta - January 17, 2019 Category: Laboratory Medicine Source Type: research