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Introduction: Duchenne muscular dystrophy (DMD) is a severe X-linked recessive neuromuscular disease that affects one in 3500 live-born males. The total absence of dystrophin observed in DMD patients is generally caused by mutations that disrupt the reading frame of the DMD gene, and about 80% of cases harbour deletions or duplications of one or more exons., Methods: We reviewed 284 cases of males with a genetic diagnosis of DMD between 2007 and 2014. These patients were selected from 8 Spanish reference hospitals representing most areas of Spain. Multiplex PCR, MLPA, and sequencing were performed to identify mutations., Results: Most of these DMD patients present large deletions (46.1%) or large duplications (19.7%) in the dystrophin gene. The remaining 34.2% correspond to point mutations, and half of these correspond to nonsense mutations. In this study we identified 23 new mutations in DMD: 7 large deletions and 16 point mutations., Conclusions: The algorithm for genetic diagnosis applied by the participating centres is the most appropriate for genotyping patients with DMD. The genetic specificity of different therapies currently being developed emphasises the importance of identifying the mutation appearing in each patient; 38.7% of the cases in this series are eligible to participate in current clinical trials., (Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.)

In 1987 a new concept in the X-linked muscular dystrophies was born with the identification of dystrophin, a cytoskeletal protein responsible for several muscular diseases previously grouped as Duchenne's or Becker's muscular dystrophies (DMD and BMD, respectively). Under the new concept these entities are referred to as dystrophinopathies. The discovery of dystrophin was made possible when polymerase chain reaction and reverse genetics opened the door to DNA examination. The DMD/BMD gene was located and sequenced and the protein product, dystrophin, was fully identified. The genetic study of dystrophinopathies was extended in the 1990's to include DNA analysis aimed at 1) discovering points of deletion or mutation that give rise to Xp21 myopathies, as dystrophinopathies are also known; 2) identifying the rules of protein translation (interruption or reading "signals" of the protein's genetic code), and 3) identifying atypical clinical phenotypes that can be diagnosed on a molecular level using anti-dystrophin antibodies or DNA probes.

DNA polymorphisms have been widely used as genetic markers for identification of the X chromosome that carries the mutation for Duchenne Muscular Dystrophy (DMD) in affected families, but serious limitations are associated with this approach. The complementary DNA (c-ADN) of the DMD gene has recently been isolated and shown to detect partial gene deletions in a large proportion of patients. We present the study of five DMD families in which we have shown the existence of a partial deletion in the DMD gene in the affected boys. We have evaluated the usefulness of this direct approach to diagnose DMD carriers in these families using the c-DNA derived probes. In all cases we have obtained satisfactory results. The method seems to be more reliable, more rapid and less expensive than linkage studies with DNA polymorphisms.