Trinucleotide repeat expansions are responsible for more than two dozens severe neurological disorders in humans. A double-strand break between two short CAG/CTG trinucleotide repeats was formerly shown to induce a high frequency of repeat contractions in yeast. Here, using a dedicated TALEN, we show that induction of a double-strand break into a CAG/CTG trinucleotide repeat in heterozygous yea...

Expanded CAG x CTG trinucleotide repeat tracts are associated with several human inherited diseases, including Huntington's disease, myotonic dystrophy, and spinocerebellar ataxias. Here we describe a new model system to investigate repeat instability in the Escherichia coli chromosome. Using this system, we reveal patterns of deletion instability consistent with secondary structure formation i...

BACKGROUND Polymorphism in the CTG triplet number in the myotonic dystrophy type 1 (DM1PK) gene has been proposed as being associated with idiopathic azoospermia. The aim of this study was to investigate whether the CTG trinucleotide amplification in the DM1PK gene is associated with male subfertility. METHODS We evaluated 107 subfertile patients, male partners of infertile couples, affected ...

Myotonic Dystrophy type 1 (DM1), the most prevalent adult onset muscular dystrophy, is a trinucleotide repeat expansion disease caused by CTG expansion in the 3'-UTR of DMPK gene. This expansion results in the expression of toxic gain-of-function RNA that forms ribonuclear foci and disrupts normal activities of RNA-binding proteins belonging to the MBNL and CELF families. Changes in alternative...

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by an expanded (CAG)n repeat on the huntingtin gene. It is characterised by motor, psychiatric and cognitive disturbances. Diagnosis can be confirmed by direct genetic testing, which is highly sensitive and specific and is now considered definitive. This study focused on 21 patients presenting with a clinical p...

PURPOSE Myotonic dystrophy type 1 (DM1) is characterized by progressive muscular weakness with symptoms caused by involvement of the brain. The aim of this study was to delineate global changes in cortical thickness and white matter integrity in patients with DM1, compared to age-matched healthy controls, and in brain areas highly correlated with CTG repeat size. MATERIALS AND METHODS Cortica...

We report two sisters with congenital myotonic dystrophy (CDM) born to a normal mother and an affected father. The congenitally affected daughters had symptoms from birth. The age of onset of DM in the father was 39 years. Analysis of the CTG trinucleotide expansion in this family showed increase in the repeat length with increasing severity, with the smallest expansion in the grandfather and t...

MOTIVATION Over a dozen major degenerative disorders, including myotonic distrophy, Huntington's disease and fragile X syndrome, result from unstable expansions of particular trinucleotides. Remarkably, only some of all the possible triplets, namely CAG/CTG, CGG/CCG and GAA/TTC, have been associated with the known pathological expansions. This raises some basic questions at the DNA level. Why d...

R-loops have been described at immunoglobulin class switch sequences, prokaryotic and mitochondrial replication origins, and disease-associated (CAG)n and (GAA)n trinucleotide repeats. The determinants of trinucleotide R-loop formation are unclear. Trinucleotide repeat expansions cause diseases including DM1 (CTG)n, SCA1 (CAG)n, FRAXA (CGG)n, FRAXE (CCG)n and FRDA (GAA)n. Bidirectional converge...

Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant cerebellar ataxia caused by a CAG repeat expansion in the ataxin-7 gene. In humans, SCA7 is characterized by marked anticipation due to intergenerational repeat instability with a bias toward expansion, and is thus regarded as the most unstable of the polyglutamine diseases. To study the molecular basis of CAG/CTG repeat instability ...