G.P.1

The phenotype of Becker muscular dystrophy (BMD) is highly variable, and thus the disorder might be underdiagnosed. In this study we have reviewed the undiagnosed cases among patients referred for suspected BMD in the period 1985–1995. At that time DNA analysis of the DMD gene was the only routinely available diagnostic test for patients suspected of having muscular dystrophy. Over the last decade sequencing techniques have been developed for the detection of small mutations in the DMD gene. Our aim was to investigate whether BMD had been genetically underdiagnosed in the early decade of DNA analysis and, if so, whether we could improve the diagnostic yield by applying new techniques. Previously, in 79 of 185 referrals for BMD testing no deletions or duplications had been found. The original requisition forms for DNA analysis were re-evaluated; Forty-six cases were excluded because clinical data were lacking or not suggestive for BMD or the patients were known to be deceased. In 33 cases the clinical information was compatible with BMD and those were considered potentially relevant for re-analysis of the DMD gene. Sequencing could be performed on 31 stored DNA samples. Six different mutations, including four novel ones, were found. Long term clinical follow-up in these adult males revealed that one patient was asymptomatic, one had mild symptoms and four had lost ambulation due to progressive limb girdle weakness. Conclusion: We conclude that extending DNA analysis by sequencing the DMD gene can be helpful in identifying BMD in male patients in whom previously no deletions or duplications were found. A delayed diagnosis can still be valuable for the proband or the relatives of the BMD patients.