title: Highly unstable sequence interruptions of the CTG repeat in the myotonic dystrophy gene.
abstract: Myotonic dystrophy type 1 is caused by the expansion of a CTG repeat in the 3' UTR of the DMPK gene. A length exceeding 50 CTG triplets is pathogenic. Intermediate alleles with 35-49 triplets are not disease-causing but show instability in intergenerational transmissions. We report on the identification of multiple patients with different patterns of CCG and CTC interruptions in the DMPK CTG repeat tract that display unique intergenerational instability. In patients bearing interrupted expanded alleles, the location of the interruptions changed dramatically between generations and the repeats tended to contract. The phenotype for these patients corresponded to the classical form of the disease, but in some cases without muscular dystrophy and possibly with a later onset than expected. Symptomatic patients bearing interrupted intermediate length repeat tracts were also identified, although the role of the interruptions in their phenotype remains unclear. The identification of interruptions in the DMPK repeat has important consequences for molecular genetic testing where they can lead to false negative conclusions.
authors.affiliation: Department of Biology and Medical Genetics, Charles University 2nd Medical School and University Hospital Motol, Prague, Czech Republic. zuzana.musova@lfmotol.cuni.cz
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Musova
authors.forename: Radim
authors.initials: R
authors.lastname: Mazanec
authors.forename: Anna
authors.initials: A
authors.lastname: Krepelova
authors.forename: Edvard
authors.initials: E
authors.lastname: Ehler
authors.forename: Jiri
authors.initials: J
authors.lastname: Vales
authors.forename: Radka
authors.initials: R
authors.lastname: Jaklova
authors.forename: Tomas
authors.initials: T
authors.lastname: Prochazka
authors.forename: Petr
authors.initials: P
authors.lastname: Koukal
authors.forename: Tatana
authors.initials: T
authors.lastname: Marikova
authors.forename: Josef
authors.initials: J
authors.lastname: Kraus
authors.forename: Marketa
authors.initials: M
authors.lastname: Havlovicova
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Sedlacek
mesh_terms: D000328:Adult; D001483:Base Sequence; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D017353:Gene Deletion; D005787:Gene Frequency; D042822:Genomic Instability / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D065636:Myotonin-Protein Kinase; D010375:Pedigree; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D018911:Trinucleotide Repeats / Q000235:genetics*; D055815:Young Adult
chemical_list: C585517:DMPK protein, human; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases