A Japanese boy with myalgia and cramps has a novel in‐frame deletion of the dystrophin gene

Abstract

We report a Japanese Becker muscular dystrophy (BMD) patient with occasional myalgia and cramps during normal activity that developed at the age of 28 months. His family history was negative for neuromuscular diseases. Muscle biopsy analyses, including dystrophin immunostaining, disclosed no clinically relevant findings. The diagnosis of BMD was initially made at the age of 10 years, when indications of persistent high serum levels of CK prompted us to screen deletions in the dystrophin gene by amplification of 19 deletion-prone exons from the genomic DNA by the polymerase chain reaction (PCR). Among the exons examined, exons 13 and 17 were deleted. To clarify the size of the deletion, the dystrophin transcript was analyzed by reverse transcription PCR. The determined nucleotide sequence of the amplified product encompassing exons 10 to 20 disclosed that the entire segment corresponding to exons 13 to 18 (810 bp) was absent, a deletion that would be expected to cause the production of a dystrophin protein lacking 270 amino acids from the rod domain. This result indicates that occasional myalgia and cramps could be early clinical manifestations of mild BMD, especially in patients who have a deletion in the rod domain, and that deletion screening of the dystrophin gene might be the only reliable method to diagnose such cases.

Entries in the Leiden Duchenne muscular dystrophy mutation database: An overview of mutation types and paradoxical cases that confirm the reading‐frame rule

“…17 Deletions removing only the first part of the central rod domain have been found in asymptomatic individuals, in persons with elevated serum creatine kinase levels, and in patients suffering from muscle cramps upon exercise. 2,24,32 In-frame deletions within exons 2-8 (the actin-binding domain) cause severe BMD, whereas deletions in the major hotspot generally cause typical BMD. 6,49 It was recently reported that deletions that include the third hinge region are generally associated with milder phenotypes than those that do not involve this hinge region.…”

Theoretic applicability of antisense-mediated exon skipping for Duchenne muscular dystrophy mutations

“…Even though the central rod domain and hinge regions that connect these essential domains are thought to be redundant, some parts are probably more important than others, and consequently, not all internally deleted dystrophins will be equally functional. In fact, in-frame deletions in the proximal regions of the central rod domain (exons 20-40) are generally milder than those in the distal part (exons 40-55) [Aartsma-Rus et al, 2006b;Angelini et al, 1994;Beggs et al, 1991;Gospe et al, 1989;Ishigaki et al, 1996]. In addition, it has been reported that the presence or absence of the hinge regions may influence functionality [Carsana et al, 2005;Yokota et al, 2007].…”

Spanish family with myalgia and cramps syndrome

“…DNA analysis revealed a deletion of exons 13-18 in the dystrophin gene. 3 In our family all the symptomatic patients had calf hypertrophy but females as well as males seemed to be affected. Three females (I,2, II,1, II,3) presented with cramps after exercise, nocturnal cramps, calf hypertrophy, and raised serum CK.…”

“…[1][2][3][4][5][6] FigarellaBranger et al 2 found five males with exercise intolerance and abnormal immunohistochemistry. DNA analysis revealed a deletion in the dystrophin gene in two of these patients, affecting the proximal part of the rod domain in one and the distal part of this domain (exons 45-52) in the other.…”