Question

N contrast to mutations associated with Duchenne muscular dystrophy, what is a feature of the mutations associated with Becker muscular dystrophy?

A They are found mostly in the 5′ region of the gene
B They are found mostly in the 3′ region of the gene
C They are unlikely to be deletions
D They are associated with some production of the dystrophin protein
E They are always point mutations

Answer 1

Mutations in the DMD gene, encoding the dystrophin protein, are responsible for the dystrophinopathies Duchenne Muscular Dystrophy (DMD), Becker Muscular Dystrophy (BMD), and X-linked Dilated Cardiomyopathy (XLDC). Mutation analysis has traditionally been challenging, due to the large gene size (79 exons over 2.2 Mb of genomic DNA). We report a very large aggregate data set comprised of DMD mutations detected in samples from patients enrolled in the United Dystrophinopathy Project, a multicenter research consortium, and in referral samples submitted for mutation analysis with a diagnosis of dystrophinopathy. We report 1111 mutations in the DMD gene, including 891 mutations with associated phenotypes. These results encompass 506 point mutations (including 294 nonsense mutations) and significantly expand the number of mutations associated with the dystrophinopathies, highlighting the utility of modern diagnostic techniques. Our data supports the uniform hypermutability of CGA>TGA mutations, establishes the frequency of polymorphic muscle (Dp427m) protein isoforms and reveals unique genomic haplotypes associated with `private' mutations. We note that 60% of these patients would be predicted to benefit from skipping of a single DMD exon using antisense oligonucleotide therapy, and 62% would be predicted to benefit from an inclusive multi-exon skipping approach directed toward exons 45 through 55.

Mutation results were derived from two cohorts. Patients in the UDP are selected by strict diagnostic criteria that include either (1) clinical features consistent with DMD or BMD and an X-linked family history; or (2) muscle biopsy showing alteration in dystrophin expression by immunofluorescence, immunohistochemistry, or immunoblot; or (3) a mutation in the DMD gene previously detected by clinical testing. After informed consent is obtained (under IRB-approved protocols), blood samples are obtained for DNA analysis; patients are examined; and data is extracted from clinical records for inclusion in the UDP database.

Answer 2

The feature of mutations associated with Becker muscular dystrophy, as opposed to Duchenne muscular dystrophy, is that they are associated with some production of the dystrophin protein.

Step-by-step explanation:

In contrast to mutations associated with Duchenne muscular dystrophy (DMD), which often involve deletions that disrupt the dystrophin protein production, a key feature of the mutations associated with Becker muscular dystrophy (BMD) is that they typically allow for some production of the dystrophin protein. While both DMD and BMD are caused by mutations in the gene that codes for dystrophin, the nature of the mutations leads to different outcomes in terms of protein production. Mutations in BMD often maintain the reading frame of the dystrophin gene, resulting in a shorter but partly functional dystrophin protein, whereas DMD mutations typically result in a complete loss of functional dystrophin.