[Frontiers in Bioscience E2, 547-558, January 1, 2010]

A 15-year molecular analysis of DMD/BMD: genetic features in a large cohort

Antonella Carsana1,2, Giulia Frisso1,2, Mariano Intrieri1,3, Maria Roberta Tremolaterra1,2, Giovanni Savarese1,2, Giovanni Scapagnini3, Gabriella Esposito1,2,4, Lucio Santoro5, Francesco Salvatore1,2

1CEINGE Biotecnologie Avanzate, Naples, Italy, 2Department of Biochemistry and Medical Biotechnology, University of Naples, Federico II, 3 Department of Health Sciences, University of Molise, Italy, 4 IRCCS, Fondazione SDN, Naples, Italy, 5Department of Neurological Sciences, University of Naples, Federico II, Italy

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Materials and methods 3.1. Patients
3.2. Methods 4. Results and Discussion 4.1. Deletions and duplications in male patients
4.2. Assessment of carrier status and prenatal diagnosis
4.3. Unbalanced X inactivation in symptomatic women 5. Conclusive remarks
6. Acknowledgements
7. References

1. ABSTRACT

Duchenne (DMD) and Becker muscular dystrophies (BMD) are X-linked recessive neuromuscular disorders caused by mutations in the dystrophin gene. In most cohorts, DMD/BMD are due to deletions (60-80%) and duplications (6-10%) involving one or more exons. The remaining cases are caused by different type of point mutations. We analyzed 179 unrelated male patients, 296 women belonging to 137 DMD/BMD families, and 93 independent patients referred for hyperCKemia. We identified 121 deletions and 11 duplications involving one or more exons and one complex rearrangement in the DMD/BMD patients, and 9 deletions in males referred for high levels of serum CK. Carrier status was investigated in 219 female relatives of deleted or duplicated DMD/BMD males, and by linkage analysis in 77 women belonging to families in which the causative mutation was not identified. Four carrier women with clinical manifestations of the disease had unbalanced X inactivation with a degree of X skewing between 70% and 93%. Large cohort studies from different geographic areas may be important for mutation typology comparisons and their appropriate analytical approach.