Maternal Carrier Status Differences in Duchenne and Becker Muscular Dystrophies

Research Article

Maternal Carrier Status Differences in Duchenne and Becker Muscular Dystrophies

Benjamin Kramer¹*, Katharina Wolf² and Laura Stein³

¹Department of Systems Biology, Technical University of Munich (TUM), Munich, Germany
²Faculty of Medicine, RWTH Aachen University, Aachen, Germany
³Department of Environmental Health, University of Leipzig, Leipzig, Germany

Published: 14 August 2020

Abstract

Background: Duchenne Muscular Dystrophy (DMD) and Becker Muscular Dystrophy (BMD) are allelic X-linked recessive disorders caused by mutations in the DMD gene, resulting in the deficiency or absence of dystrophin, a protein essential for muscle function. These conditions primarily affect males, but carrier females can exhibit a spectrum of symptoms ranging from asymptomatic to manifesting carriers with muscle weakness. Accurate identification of carrier status in female relatives, particularly mothers, is essential for genetic counseling, reproductive decision-making, and early intervention. Previous studies suggested a potential difference in the carrier frequency among mothers of affected males, with a lower carrier rate observed in mothers of DMD patients compared to those of BMD patients.

Objective: The aim of this study was to investigate the carrier status among mothers of male patients with DMD and BMD, and to explore the potential reasons for the observed differences in carrier rates between the two conditions. The study also aimed to assess the genetic implications of these findings in terms of reproductive counseling and early diagnosis.

Methods: The study involved clinical observations and genetic analysis of female relatives of male patients diagnosed with either DMD or BMD. Carrier status was determined using molecular genetic testing to identify mutations in the DMD gene. The frequency of carrier status was compared between mothers of DMD patients and mothers of BMD patients. De novo mutation rates and reproductive histories of affected males were also examined to assess potential factors influencing carrier transmission.

Results: Our findings confirmed a lower carrier rate in mothers of DMD patients compared to mothers of BMD patients. This difference was primarily attributed to the higher frequency of de novo mutations in DMD, which leads to the severe phenotype that often prevents reproduction in affected males. In contrast, the milder phenotype of BMD allows a larger proportion of affected males to reproduce, increasing the likelihood of the transmission of mutations from carrier mothers to their offspring.

Conclusion: This study highlights the importance of understanding the genetic dynamics of DMD and BMD in the context of carrier status. The observed differences in carrier frequency suggest that genetic counseling for families of affected males should take into account the potential for de novo mutations in DMD and inherited mutations in BMD. Early identification of carrier females is crucial for appropriate clinical management, reproductive planning, and intervention strategies in both DMD and BMD.

Keywords: Duchenne muscular dystrophy; Becker muscular dystrophy; DMD gene; Dystrophin; X-linked inheritance; Carrier detection; Carrier frequency; de novo mutation; Genetic counseling; Dystrophinopathy