title: Development of a genomic DNA reference material panel for myotonic dystrophy type 1 (DM1) genetic testing.
abstract: Myotonic dystrophy type 1 (DM1) is caused by expansion of a CTG triplet repeat in the 3' untranslated region of the DMPK gene that encodes a serine-threonine kinase. Patients with larger repeats tend to have a more severe phenotype. Clinical laboratories require reference and quality control materials for DM1 diagnostic and carrier genetic testing. Well-characterized reference materials are not available. To address this need, the Centers for Disease Control and Prevention-based Genetic Testing Reference Material Coordination Program, in collaboration with members of the genetic testing community, the National Registry of Myotonic Dystrophy and Facioscapulohumeral Muscular Dystrophy Patients and Family Members, and the Coriell Cell Repositories, has established and characterized cell lines from patients with DM1 to create a reference material panel. The CTG repeats in genomic DNA samples from 10 DM1 cell lines were characterized in three clinical genetic testing laboratories using PCR and Southern blot analysis. DMPK alleles in the samples cover four of five DM1 clinical categories: normal (5 to 34 repeats), mild (50 to 100 repeats), classical (101 to 1000 repeats), and congenital (>1000 repeats). We did not identify or establish Coriell cell lines in the premutation range (35 to 49 repeats). These samples are publicly available for quality control, proficiency testing, test development, and research and should help improve the accuracy of DM1 testing.
authors.affiliation: Division of Laboratory Science and Standards, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA. lkalman@cdc.gov
authors.forename: Lisa
authors.initials: L
authors.lastname: Kalman
authors.forename: Jack
authors.initials: J
authors.lastname: Tarleton
authors.forename: Monica
authors.initials: M
authors.lastname: Hitch
authors.forename: Madhuri
authors.initials: M
authors.lastname: Hegde
authors.forename: Nick
authors.initials: N
authors.lastname: Hjelm
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Berry-Kravis
authors.forename: Lili
authors.initials: L
authors.lastname: Zhou
authors.forename: James E
authors.initials: JE
authors.lastname: Hilbert
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Luebbe
authors.forename: Richard T
authors.initials: RT
authors.lastname: Moxley
authors.forename: Lorraine
authors.initials: L
authors.lastname: Toji
mesh_terms: D000483:Alleles; D002460:Cell Line; D004247:DNA / Q000235:genetics; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D009223:Myotonic Dystrophy / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases / Q000097:blood / Q000235:genetics* / Q000302:isolation & purification; D012015:Reference Standards; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*
chemical_list: C585517:DMPK protein, human; D004247:DNA; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases