Correlation of genotypes and phenotypes in patients with Duchenne and Becker muscular dystrophy caused by deletions in the dystrophine gene
Abstract
The correlation between genotype and phenotype has been studied in 20 patients with Duchenne or Becker muscular dystrophy (DMD or BMD) with deletions in the dystrophine gene. In an agreement with the known theory the authors accept that frameshift deletions cause MM whereas in-frame deletions produce BMD.
According to clinical symptoms BMD has been diagnosed in 5 patients and DMD in 15 patients. While determining the extent of deletions by PCR the authors have anticipated that deletion breakpoints in patients are between two neighbouring exons one of which has been detected by PCR but the other one has not.
Out of a group of 20 patients 5 have been diagnosed with the in-frame deletions, 14 with frameshift deletions. In one DMD patient two deletions have been detected, one of them being in-frame one and the other a frameshift one.
While comparing genotypes and phenotypes of the examined patients no complete correlation has been found. In 4 patients with the clinical symptoms of BMD the reading frame of a dystrophine gene has been preserved but in one patient it has been changed.
In 14 DMD patients the reading frame has been destructed but in one case it has been preserved. This way the correlation between genotypes and phenotypes has equalled 90 percent.
This close correlation is in an agreement with the theory that frameshift mutations lead to a DMD phenotype whereas in-frame mutations cause a milder BMD phenotype. In 2 patients (10 per cent) where diagnosed mutations did not correlate with clinical symptoms hypotheses have been proposed which could clear up discrepancies between genotype and phenotype.
To explain these discrepancies, other (undetected) mutations in the dystrophin gene, aberrant splicing of dystrophine mRNA, reinitiation of a translation from an alternative promoter, location of breakpoints off the respective introns and instability of transcribed or translated product have been submitted for consideration. To make an unambiguous conclusion in patients with the discrepancies between their genotype and phenotype an investigation of mRNA or protein levels is necessary.