Detection of truncated dystrophin in fetal DMD myotubes

Adv Exp Med Biol. 1990:280:17-23. doi: 10.1007/978-1-4684-5865-7_4.

Abstract

An immunohistochemical study was carried out on a twelve-week old fetus, aborted for high risk of Duchenne muscular dystrophy. Southern and FIGE analysis showed an intragenic duplication in the DMD gene, which had previously resulted in a severe Duchenne phenotype in three relatives. Polyclonal antibodies directed against the NH2-terminal half of dystrophin showed a positive reaction an a similar distribution of dystrophin in the skeletal myotubes of a twelve-week old normal fetus and the affected fetus. In contrast, a polyclonal antibody directed against the COOH-terminus of dystrophin, i.e., distal to the mutation in this family, did only react with the myotubes of the normal fetus and not with those of the affected fetus. This indicates the presence of a truncated dystrophin in the affected fetus. Apparently at this stage, before binding of dystrophin to the sarcolemma, no distinction is made yet between normal and abnormal dystrophins. This implies that the potential to bind to the sarcolemma could be a major point of discrimination between normal and defective dystrophins. The truncated dystrophin will probably be degraded in a later stage during fetal development. So it appears that the use of dystrophin immunostaining to confirm high Duchenne risk abortions requires great caution. To prevent false-positive results, the combined use of NH2- and COOH-terminal antibodies is mandatory.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dystrophin / genetics
  • Dystrophin / metabolism*
  • Fetus / metabolism
  • Humans
  • Immunohistochemistry
  • Male
  • Muscles / metabolism
  • Muscular Dystrophies / genetics
  • Muscular Dystrophies / metabolism*
  • Pedigree

Substances

  • Dystrophin