UCL logo

UCL Discovery

UCL home » Library Services » Electronic resources » UCL Discovery

Absence of neuronal nitric oxide synthase (nNOS) as a pathological marker for the diagnosis of Becker muscular dystrophy with rod domain deletions

Torelli, S; Brown, SC; Jimenez-Mallebrera, C; Feng, L; Muntoni, F; Sewry, CA; (2004) Absence of neuronal nitric oxide synthase (nNOS) as a pathological marker for the diagnosis of Becker muscular dystrophy with rod domain deletions. NEUROPATH APPL NEURO , 30 (5) 540 - 545. 10.1111/j.1365-2990.2004.00561.x.

Full text not available from this repository.

Abstract

Immunohistochemistry using antibodies to dystrophin is the pathological basis for the diagnosis of Duchenne and Becker muscular dystrophy (DMD and BMD). While the sarcolemma of DMD muscle is negative, BMD muscle generally shows variable labelling because of the translation of a partially functional dystrophin that is localized to the sarcolemma. In rare cases, however, this labelling is equivocal and similar to that observed in controls making diagnosis difficult. We report here that in such instances immunolabelling with antibodies to the neuronal form of nitric oxide synthase (nNOS) can be useful in suspecting a dystrophinopathy with a mutation in the 'hot-spot' rod domain and help to direct molecular analysis. nNOS localizes to the sarcolemma of mature muscle fibres via several components of the dystrophin-associated protein complex (DAPC) including dystrophin but sarcolemmal nNOS is lost when dystrophin levels are very low or absent because of deletions in critical regions of the rod domain. We report three cases who presented with only mild or no muscle weakness but had elevated serum creatine kinase activity and dystrophin immunolabelling indistinguishable from normal, making a pathological diagnosis difficult. All three cases had a complete absence of sarcolemmal nNOS and were subsequently found to have an in-frame deletion in the common rod domain exons (in these cases 48, 45-51, 47-53) compatible with a BMD. In addition, we observed that nNOS appears to be developmentally regulated with the antibody used and was often absent from the sarcolemma of immature fibres. These findings demonstrate the value of including antibodies to nNOS in routine immunohistochemical studies and that absence of nNOS can be a more sensitive marker than up-regulation of utrophin for diagnosis of BMD. Immaturity of fibres, however, needs to be taken into account, especially in neonates.

Type: Article
Title: Absence of neuronal nitric oxide synthase (nNOS) as a pathological marker for the diagnosis of Becker muscular dystrophy with rod domain deletions
DOI: 10.1111/j.1365-2990.2004.00561.x
Keywords: Becker muscular dystrophy, diagnosis, dystrophin, nNOS, SKELETAL-MUSCLE, DUCHENNE, SARCOLEMMA
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health > ICH Developmental Neurosciences Prog
URI: http://discovery.ucl.ac.uk/id/eprint/125808
Downloads since deposit
0Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item