Sporadic occurrence of Duchenne Muscular Dystrophy: evidence for new mutation

Abstract

The mechanism of inheritance of sporadically occurring Duchenne muscular dystrophy has been investigated in 42 families, using carrier detection methods and genetic evaluation. Our studies find that serum CPK detects 72 % of female carriers of DMD. Quantitative LDH and/or its isozymes were not found to be a useful means of carrier detection, as reported by Roses et al. (1977). Employing family pedigree data and CPK carrier testing, we determined by Bayesian methods the probability that the mother and maternal grandmother in these families were DMD carriers. These studies revealed 23 families (Category I) with no evidence for DMD carriers, 11 families (Category 11) in which the mother was found to be a carrier, and 3 families (Category III) in which both mother and maternal grandmother were found to be carriers. Nineteen of the 42 families have a greater than 83 % probability that the sporadic DMD case arose by mutation in a maternal gamete. This finding is in good agreement with the theoretically expected ⅓ of DMD cases arising by new mutation.

Prenatal diagnosis of duchenne/becker muscular dystrophy by short tandem repeat segregation analysis in argentine families

“…The certainty of being a DMD carrier was 95%, so there is a 5% chance that the mutation would not be linked to the at‐risk haplotype because of a recombination event.In families 4(III1 and III2) and 11(III1), each with a sporadic case, the fetus and the DMD patients shared the same haplotype, thus the risk of inheriting the maternal mutation would be 67%, because two thirds of DMD cases are transmitted. This would be approximately the probability of the fetuses being carriers 1, 2 Families with a non‐informative or inconclusive diagnosis .…”

“…DMD is the most common X‐linked recessive lethal disorder with an incidence of ∽1 in 3500 newborns. Approximately one third of the cases result from de novo mutations in the dystrophin gene located at the Xp21 region 1–4. Intragenic deletions and duplications together account for over two thirds of the mutations that cause DMD/BMD; the remaining cases are due to point mutations or small insertions/deletions distributed along the entire gene 5.…”

Canine models of Duchenne muscular dystrophy and their use in therapeutic strategies

“…A recent study in which point mutations identified by sequence analysis were likely over represented found an incidence of only 43% deletions, 11% duplications, and 46% point mutations (Flanigan et al 2009). While DMD classically demonstrates a strong family history, about one third of cases occur due to new mutations (Caskey et al 1980). …”

Identification of de novo Mutations of Duchénnè/Becker Muscular Dystrophies in Southern Spain

“…Findings since that date have been controversial, with a similar frequency being reported by some authors 21 but a higher 22 or lower frequency (around 20%) 23 by others. A sporadic mutation was detected in 16.7% of the present series of DMD/BMD patients.…”

“…It has been known since 1987 that DMD/BMD is caused by mutations of the DMD gene, the largest known human gene (2.4 Mb and 79 exons) 20, 21. The recently developed MLPA assay 14, 15 allows deletions and duplications to be detected in any of the 79 exons of this gene.…”