Alternative splicing ofdystrophin mRNA complicates carrier determination: reportofa DMD family

Carrierdetermination isimportantfor genetic counselling inDMD/BMD families. Thedetection ofaltered PCR amplifieddystrophin mRNA fragmentsowing todeletions, insertions, orpointmutationshasincreased thepossibilities of carrier determination. However,problemsmay occurbecauseofalternative splicing events. Herewepresent afamily witha DMD patient characterised bya deletion ofexons45to54.AtthemRNA level wedetected acorresponding altered fragmentwhichservedforcarrier determination. Themotherandthesister of thepatient showedthesamealtered dystrophin mRNA fragmentasthepatient andaretherefore carriers. Inthemother twoadditional altered dystrophin mRNA fragmentswere detectable, obviously resulting fromalternative splicing inthe normalallele. Thegrandmother andtwo otherrelated femalesofthepatient possessonlythenormalmRNA fragment. In a further femalewe detected analtered fragmentowingtoanmRNA deletion of exon44.Thisfragmentiscreated either byalternative splicing ora new mutation.Therefore, thecarrierstatusof thisfemaleisstill ambiguousindicating problems incarrier determination bythe methodofdystrophin mRNA analysis. (7MedGenet 1993;30:206-9)