Background & Aims: Nearly 30 hereditary disorders in humans result from an increase in the number of copies of simple repeats in genomic DNA, including fragile X syndrome, myotonic dystrophy, Huntington’s disease, and Friedreich’s ataxia. One the most frequently occurring types of mutation is trinucleotide repeat expansion. The present study was conducted with the aim of investigating the cause...

Expansions of simple DNA repeats are responsible for more than two dozen hereditary disorders in humans, including fragile X syndrome, myotonic dystrophy, Huntington's disease, various spinocerebellar ataxias, Friedreich's ataxia and others. During the past decade, it became clear that unusual structural features of expandable repeats greatly contribute to their instability and could lead to th...

Expansions of simple DNA repeats cause numerous hereditary diseases in humans. We analyzed the role of DNA polymerases in the instability of Friedreich's ataxia (GAA)(n) repeats in a yeast experimental system. The elementary step of expansion corresponded to ~160 bp in the wild-type strain, matching the size of Okazaki fragments in yeast. This step increased when DNA polymerase α was mutated, s...

Spinocerebellar ataxia 10 (SCA10) is an autosomal dominant disease caused by large-scale expansions of the (ATTCT)(n) repeat within an intron of the human ATXN10 gene. In contrast to other expandable repeats, this pentanucleotide repeat does not form stable intra- or interstranded DNA structures, being a DNA unwinding element instead. We analyzed the instability of the (ATTCT)(n) repeat in a ye...

OBJECTIVE To evaluate the reasons for repeat intervention in patients treated with balloon expandable stents for pulmonary artery stenoses, with particular analysis of the time intervals between interventions. DESIGN A retrospective observational study. SETTING A single paediatric cardiology centre. PATIENTS 38 patients, mean age 6.9 years, range 6 days to 34 years (one adult patient); me...

Objective: To evaluate the reasons for repeat intervention in patients treated with balloon expandable stents for pulmonary artery stenoses, with particular analysis of the time intervals between interventions. Design: A retrospective observational study. Setting: A single paediatric cardiology centre. Patients: 38 patients, mean age 6.9 years, range 6 days to 34 years (one adult patient); mean...

Expansions of triplet repeats are responsible for more than 15 hereditary neurological disorders in humans. Triplet repeats are fairly stable when the number of elementary units is under approx 30, but become polymorphic in length with a clear bias for expansions when this threshold is exceeded. This results in the rapid addition of hundreds or even thousands of extra repeats and, ultimately, d...

Atypical DNA secondary structures play an important role in expandable trinucleotide repeat (TR) and hexanucleotide repeat (HR) diseases. The cytosine mismatches in C-rich homoduplexes and hairpin stems are weakly bonded; experiments show that for certain sequences these may flip out of the helix core, forming an unusual structure termed an 'e-motif'. We have performed molecular dynamics simula...

A 56-year-old male with metastatic unresectable cholangiocarcinoma presented to our clinic with worsening nausea and vomiting. Prior to presentation, the patient underwent placement of a palliative metal biliary stent and an uncovered self-expandable metal stents (UCSEMS) through the pylorus and duodenum for gastric outlet obstruction (GOO) from tumor burden. However, the patient subsequently d...