TY - JOUR
T1 - Immunohistological evidence for second or somatic mutations as the underlying cause of dystrophin expression by isolated fibres in Xp21 muscular dystrophy of Duchenne-type severity
AU - Wallgren-Pettersson, Carina
AU - Jasani, Bharat
AU - Rosser, Lyndon G.
AU - Lazarou, Lazarus Pavlou
AU - Nicholson, Louise V.B.
AU - Clarke, Angus
PY - 1993/8
Y1 - 1993/8
N2 - Using five monoclonal antibodies against different parts of the dystrophin molecule, we have studied the dystrophin composition of 17 dystrophin-positive fibres in a muscle biopsy from a boy with Xp21 muscular dystrophy of Duchenne-type severity. The fibres showed five distinct, reproducible, immunoreactive dystrophin profiles. All the profiles included both the N-terminal and the C-terminal domains, but between these domains, different fibres were negative for different antibodies, suggesting the somatic loss of certain exons. We interpret this as the first in situ evidence of an individual having different patterns of missing exons leading to restoration of the reading frame in various ways in the original germline frame-shifting deletion of exons 35-43. It follows that various somatic mutations had taken place in different fibres.
AB - Using five monoclonal antibodies against different parts of the dystrophin molecule, we have studied the dystrophin composition of 17 dystrophin-positive fibres in a muscle biopsy from a boy with Xp21 muscular dystrophy of Duchenne-type severity. The fibres showed five distinct, reproducible, immunoreactive dystrophin profiles. All the profiles included both the N-terminal and the C-terminal domains, but between these domains, different fibres were negative for different antibodies, suggesting the somatic loss of certain exons. We interpret this as the first in situ evidence of an individual having different patterns of missing exons leading to restoration of the reading frame in various ways in the original germline frame-shifting deletion of exons 35-43. It follows that various somatic mutations had taken place in different fibres.
KW - Duchenne muscular dystrophy
KW - Frame-shift deletion
KW - Immunocytochemistry
KW - Immunoreactive dystrophin
KW - Revertant fibre
KW - Somatic mutation
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U2 - 10.1016/0022-510X(93)90246-U
DO - 10.1016/0022-510X(93)90246-U
M3 - Article
C2 - 8229051
AN - SCOPUS:0027183926
VL - 118
SP - 56
EP - 63
JO - Journal of the Neurological Sciences
JF - Journal of the Neurological Sciences
SN - 0022-510X
IS - 1
ER -