Mutations in the DMD gene, encoding the dystrophin protein, are responsible for the dystrophinopathies Duchenne Muscular Dystrophy (DMD), Becker Muscular Dystrophy (BMD), and X-linked Dilated Cardiomyopathy (XLDC). Mutation analysis has traditionally been challenging, due to the large gene size (79 exons over 2.2 Mb of genomic DNA). We report a very large aggregate data set comprised of DMD mutations detected in samples from patients enrolled in the United Dystrophinopathy Project, a multicenter research consortium, and in referral samples submitted for mutation analysis with a diagnosis of dystrophinopathy. We report 1111 mutations in the DMD gene, including 891 mutations with associated phenotypes. These results encompass 506 point mutations (including 294 nonsense mutations) and significantly expand the number of mutations associated with the dystrophinopathies, highlighting the utility of modern diagnostic techniques. Our data supports the uniform hypermutability of CGA>TGA mutations, establishes the frequency of polymorphic muscle (Dp427m) protein isoforms and reveals unique genomic haplotypes associated with `private' mutations. We note that 60% of these patients would be predicted to benefit from skipping of a single DMD exon using antisense oligonucleotide therapy, and 62% would be predicted to benefit from an inclusive multi-exon skipping approach directed toward exons 45 through 55.

The stages in adolescent slipping of the upper femoral epiphysis are classified in relation to treatment. The operation of open replacement of the displaced femoral head is described, and the results of a personal series of seventy-three such operations are presented. Open replacement is excellent treatment for severe chronic slipping so long as the growth plate is still open. The greater incidence of avascular necrosis in acute-on-chronic cases is probably due to damage to the blood supply of the head at the time of the acute slip or kinking of the vessels before replacement. Prolonged traction before operation may increase the risk of chondrolysis. Late onset of osteoarthritis when neither avascular necrosis nor chondrolysis has occurred may be due to misfitting of the articular cartilage because of inaccurate reduction.

The results of open reduction of the severely slipped upper femoral epiphysis are reported for 1 15 hips with an average follow-up of 12 years 11 months (range 2 to 33 years). In 70 hips with a chronic slip and an open growth plate the incidence of complications was low: two developed avascular necrosis, five chondrolysis, and one had both. There were more complications in the 38 hips with an acute-on-chronic slip: six developed avascular necrosis, one chondrolysis, and three had both. Of the seven hips operated upon with a partially fused plate, only one did well. All these complications were obvious within the first year but there were also three hips in the series in which osteoarthritis developed between 10 and 20 years after operation.

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