The TREAT-NMD DMD Global Database: analysis of more than 7,000 Duchenne muscular dystrophy mutations

Hum Mutat. 2015 Apr;36(4):395-402. doi: 10.1002/humu.22758. Epub 2015 Mar 17.

Abstract

Analyzing the type and frequency of patient-specific mutations that give rise to Duchenne muscular dystrophy (DMD) is an invaluable tool for diagnostics, basic scientific research, trial planning, and improved clinical care. Locus-specific databases allow for the collection, organization, storage, and analysis of genetic variants of disease. Here, we describe the development and analysis of the TREAT-NMD DMD Global database (http://umd.be/TREAT_DMD/). We analyzed genetic data for 7,149 DMD mutations held within the database. A total of 5,682 large mutations were observed (80% of total mutations), of which 4,894 (86%) were deletions (1 exon or larger) and 784 (14%) were duplications (1 exon or larger). There were 1,445 small mutations (smaller than 1 exon, 20% of all mutations), of which 358 (25%) were small deletions and 132 (9%) small insertions and 199 (14%) affected the splice sites. Point mutations totalled 756 (52% of small mutations) with 726 (50%) nonsense mutations and 30 (2%) missense mutations. Finally, 22 (0.3%) mid-intronic mutations were observed. In addition, mutations were identified within the database that would potentially benefit from novel genetic therapies for DMD including stop codon read-through therapies (10% of total mutations) and exon skipping therapy (80% of deletions and 55% of total mutations).

Keywords: DMD; Duchenne muscular dystrophy; TREAT-NMD; rare disease registries.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Databases, Genetic*
  • Dystrophin / genetics*
  • Humans
  • Muscular Dystrophy, Duchenne / genetics*
  • Mutation*
  • Registries

Substances

  • Dystrophin