mal creatine kinase. Clinical cardiological examination and echocardiography were normal but electrocardiography showed arteriovenous block I and left anterior hemiblock. Molecular genetic analysis revealed a CTG expansion of 130 repeats in the DMPK gene. The diagnosis of DM1 was established. After the last episode of gluteal erysipelas in September 2005, she underwent a long-term oral penicill...

A dozen dominant genetic disorders are caused by aberrant expansions of CAG or CTG trinucleotide repeats. As these repeats are complementary sequences, the expansions are incurred by both strands. However, it is the genic or transcribed strand that has defined the CAG and CTG repeat diseases. CAG repeat–associated diseases represent a group of neurological disorders, including Huntington’s dise...

Unusual DNA secondary structures have been implicated in the expansion of trinucleotide repeat tracts that are associated with several human inherited disorders. We present evidence consistent with the folding of these trinucleotide repeats into hairpin loops at the center of a long DNA palindrome in vivo. Our assay utilizes a palindrome in bacteriophage lambda, the center of which determines i...

Myotonic dystrophy type 1 (DM1) is caused by the expansion of an unstable CTG repeat located in the 3'-UTR of (DMPK) the DM protein kinase gene. Patients with DM1 have expansions of greater than 50 repeats and up to many thousands. In the present study we aimed to evaluate the utility of TP-PCR in diagnostics as well as the assessment of premutation carriers in proband families. Twenty-seven DM...

Purpose Studies of Fuchs' dystrophy have largely focused on individuals of European origin. Characterization of disease among African Americans is required to ensure prognostic factors and therapeutic approaches are applicable across diverse patient populations. Methods We assessed all self-reported black and white patients aged older than 40 years at a tertiary care institution with a diagno...

We report here a simple method for generating large CAG/CTG repeat sequences. We have applied this method to clone the genomic sequence containing the CAG/CTG repeat and its upstream intronic sequence present in spinocerebellar ataxia type 3 or Machado-Joseph disease (SCA3/MJD) by a modified DIRECT method. With these modifications we have considerably simplified the generation of the repeat pro...

Trinucleotide repeat (TNR) expansions are the underlying cause of more than 40 neurodegenerative and neuromuscular diseases, including myotonic dystrophy and Huntington's disease, yet the pathway to expansion remains poorly understood. An important step in expansion is the shift from a stable TNR sequence to an unstable, expanding tract, which is thought to occur once a TNR attains a threshold ...

The autosomal dominant mutation causing myotonic dystrophy (DM1) is a CTG repeat expansion in the 3'-UTR of the DM protein kinase (DMPK) gene. This multisystemic disorder includes myotonia, progressive weakness and wasting of skeletal muscle and extramuscular symptoms such as cataracts, testicular atrophy, endocrine and cognitive dysfunction. The mechanisms underlying its pathogenesis are compl...

A (CTG)nexpansion in the 3'-untranslated region (UTR) of the DM protein kinase gene ( DMPK ) is responsible for causing myotonic dystrophy (DM). Major instability, with very large expansions between generations and high levels of somatic mosaicism, is observed in patients. There is a good correlation between repeat size (at least in leucocytes), clinical severity and age of onset. The trinucleo...