Highly unstable sequence interruptions of the CTG repeat in the myotonic dystrophy gene

• Published in: American journal of medical genetics. Part A Vol. 149A; no. 7; pp. 1365 - 1374
• Main Authors: Musova, Zuzana, Mazanec, Radim, Krepelova, Anna, Ehler, Edvard, Vales, Jiri, Jaklova, Radka, Prochazka, Tomas, Koukal, Petr, Marikova, Tatana, Kraus, Josef, Havlovicova, Marketa, Sedlacek, Zdenek
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.07.2009; Wiley-Liss
• Subjects: Adult; Base Sequence; Biological and medical sciences; Case-Control Studies; CTG repeat; Diseases of striated muscles. Neuromuscular diseases; DMPK gene; DNA Mutational Analysis; Family; Female; Gene Deletion; Gene Frequency; Genomic Instability - physiology; Humans; interruptions; Male; Medical genetics; Medical sciences; Middle Aged; myotonic dystrophy; Myotonin-Protein Kinase; Neurology; Pedigree; Protein-Serine-Threonine Kinases - genetics; Trinucleotide Repeats - genetics; Young Adult; CTG repeat; Nervous system diseases; Neuromuscular diseases; Interruption; Myotonic dystrophy; Gene; Myotonia; Repeated sequence; interruptions; DMPK gene; Instability; Genetic disease
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.32987

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. © 2009 Wiley‐Liss, Inc.