An inherited dystrophin deletion without muscle weakness.

An inherited dystrophin deletion without muscle weakness Deletions of the dystrophin gene are known to be present in approximately 60 to 70%6 of Duchenne (DMD) and Becker (BMD) patients. We describe a boy and his maternal grandfather who both have raised creatine kinase levels and an identical deletion including exons 14-18 of the dystrophin gene but no muscle weakness. Muscle histology is normal in the boy. A previously well 5 year old boy presented with a three year history of occasional muscle cramps in his legs after exercise. On examination he had no calf hypertrophy or muscle weakness and Gower's sign was negative. However, his creatine kinase (CK) was grossly raised at 7854 IU 1 (NR 1-220 IU 1) and a diagnosis of DMD was suspected. Examination by a paediatric neurologist confirmed normal power, tone, reflexes, and muscle bulk. Two further CK measurements were also raised at 6253 IU 1 and 11 800 IU 1 (NR 25-195). A quadriceps muscle biopsy was histolo-gically normal with little variation in fibre size and no evidence of muscle fibre regeneration or destruction. There was good fibre type differentiation and no evidence of denervation or congenital myopathy. Immunocytochemistry for dystro-phin DYS1 and DYS2 antibodies was normal. The boy's mother had no muscle related symptoms and a normal CK (101 IU 1) but reported that her father suffered from muscle pains when young. On questioning he remembered having pains in his legs as a child and still had aching of his limbs after exertion. However, he had coped with physically demanding jobs throughout his life. A creatine kinase level in him was also raised at 520 IU 1 (NR 1-220 IU 1). DNA analysis by Southern blotting using standard techniques' was carried out using DNA probes specific to dystrophin gene exons.23 Both the proband and his grandfather showed a deletion with probe 2b-3 spanning exons 14-18 of the dystrophin gene. Exons 13 and 19 were present. Such a deletion would not be expected to disrupt the reading frame.4 Western blot analysis of a muscle biopsy from the proband using antibodies corresponding to exons 25-30 and 55-60 (which are distal to the deletion) showed both of these parts of the dystrophin gene to be present. This is also consistent with a deletion which does not disrupt the gene reading frame. Both antibodies detected reduced abundance of dystrophin (-60%) of slightly reduced molecular weight, 20 Kda or …