RT Journal Article
SR Electronic
T1 Clinical characterisation of Becker muscular dystrophy patients predicts favourable outcome in exon-skipping therapy
JF Journal of Neurology, Neurosurgery & Psychiatry
JO J Neurol Neurosurg Psychiatry
FD BMJ Publishing Group Ltd
SP 92
OP 98
DO 10.1136/jnnp-2012-304729
VO 85
IS 1
A1 J C van den Bergen
A1 S M Schade van Westrum
A1 L Dekker
A1 A J van der Kooi
A1 M de Visser
A1 B H A Wokke
A1 C S Straathof
A1 M A Hulsker
A1 A Aartsma-Rus
A1 J J Verschuuren
A1 H B Ginjaar
YR 2014
UL http://jnnp.bmj.com/content/85/1/92.abstract
AB Objective Duchenne and Becker muscular dystrophy (DMD/BMD) are both caused by mutations in the DMD gene. Out-of-frame mutations in DMD lead to absence of the dystrophin protein, while in-frame BMD mutations cause production of internally deleted dystrophin. Clinically, patients with DMD loose ambulance around the age of 12, need ventilatory support at their late teens and die in their third or fourth decade due to pulmonary or cardiac failure. BMD has a more variable disease course. The disease course of patients with BMD with specific mutations could be very informative to predict the outcome of the exon-skipping therapy, aiming to restore the reading-frame in patients with DMD. Methods Patients with BMD with a mutation equalling a DMD mutation after successful exon skipping were selected from the Dutch Dystrophinopathy Database. Information about disease course was gathered through a standardised questionnaire. Cardiac data were collected from medical correspondence and a previous study on cardiac function in BMD. Results Forty-eight patients were included, representing 11 different mutations. Median age of patients was 43 years (range 6–67). Nine patients were wheelchair users (26–56 years). Dilated cardiomyopathy was present in 7/36 patients. Only one patient used ventilatory support. Three patients had died at the age of 45, 50 and 76 years, respectively. Conclusions This study provides mutation specific data on the course of disease in patients with BMD. It shows that the disease course of patients with BMD, with a mutation equalling a ‘skipped’ DMD mutation is relatively mild. This finding strongly supports the potential benefit of exon skipping in patients with DMD.