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J Mol Diagn 2021 Feb 19. Epub 2021 Feb 19.

Khoo Teck Puat - National University Children's Medical Institute, National University Health System, 119228, Singapore; Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, 119228, Singapore; Department of Laboratory Medicine, National University Hospital, 119074, Singapore. Electronic address:

The autosomal-dominantly inherited spinocerebellar ataxias (SCAs) can be caused by dynamic mutations of short tandem repeats within various genes. Due to the significant clinical overlap among the various SCA types, molecular screening of multiple genetic loci by fluorescent PCR and capillary electrophoresis is necessary to identify the causative repeat expansion. We describe a simple, rapid, and inexpensive strategy to screen for CAG repeat expansion mutations at the ATXN1, ATXN2, and ATXN3 loci using melting curve analysis (MCA) of triplet-primed PCR products. Read More

Front Cell Neurosci 2020 2;14:606331. Epub 2021 Feb 2.

Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.

More than 30 human disorders are caused by the expansion of simple sequence DNA repeats, among which triplet repeats remain the most frequent. Most trinucleotide repeat expansion disorders affect primarily the nervous system, through mechanisms of neurodysfunction and/or neurodegeneration. While trinucleotide repeat tracts are short and stably transmitted in unaffected individuals, disease-associated expansions are highly dynamic in the germline and in somatic cells, with a tendency toward further expansion. Read More

J Huntingtons Dis 2021 ;10(1):75-94

Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, PA, USA.

DNA mismatch repair (MMR) is a highly conserved genome stabilizing pathway that corrects DNA replication errors, limits chromosomal rearrangements, and mediates the cellular response to many types of DNA damage. Counterintuitively, MMR is also involved in the generation of mutations, as evidenced by its role in causing somatic triplet repeat expansion in Huntington's disease (HD) and other neurodegenerative disorders. In this review, we discuss the current state of mechanistic knowledge of MMR and review the roles of key enzymes in this pathway. Read More

Int J Mol Sci 2021 Feb 8;22(4). Epub 2021 Feb 8.

Huntington and Rare Diseases Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy.

The expanded CAG repeat number in gene causes Huntington disease (HD), which is a severe, dominant neurodegenerative illness. The accurate determination of the expanded allele size is crucial to confirm the genetic status in symptomatic and presymptomatic at-risk subjects and avoid genetic polymorphism-related false-negative diagnoses. Precise CAG repeat number determination is critical to discriminate the cutoff between unexpanded and intermediate mutable alleles (IAs, 27-35 CAG) as well as between IAs and pathological, low-penetrance alleles (i. Read More

Front Mol Neurosci 2020 11;13:617229. Epub 2021 Jan 11.

QPS Austria GmbH, Grambach, Austria.

Huntington's disease (HD) is caused by an expansion of CAG triplets in the huntingtin gene, leading to severe neuropathological changes that result in a devasting and lethal phenotype. Neurodegeneration in HD begins in the striatum and spreads to other brain regions such as cortex and hippocampus, causing motor and cognitive dysfunctions. To understand the signaling pathways involved in HD, animal models that mimic the human pathology are used. Read More