Neurological disorders caused by novel non-coding repeat expansions: clinical features and differential diagnosis

Elisa Vegezzi; Hiroyuki Ishiura; D Cristopher Bragg; David Pellerin; Francesca Magrinelli; Riccardo Currò; Stefano Facchini; Arianna Tucci; John Hardy; Nutan Sharma; Matt C Danzi; Stephan Zuchner; Bernard Brais; Mary M Reilly; Shoji Tsuji; Henry Houlden; Andrea Cortese

doi:10.1016/S1474-4422(24)00167-4

Neurological disorders caused by novel non-coding repeat expansions: clinical features and differential diagnosis

Lancet Neurol. 2024 Jul;23(7):725-739. doi: 10.1016/S1474-4422(24)00167-4.

Authors

Elisa Vegezzi¹, Hiroyuki Ishiura², D Cristopher Bragg³, David Pellerin⁴, Francesca Magrinelli⁵, Riccardo Currò⁶, Stefano Facchini⁷, Arianna Tucci⁸, John Hardy⁹, Nutan Sharma³, Matt C Danzi¹⁰, Stephan Zuchner¹⁰, Bernard Brais¹¹, Mary M Reilly¹², Shoji Tsuji¹³, Henry Houlden¹², Andrea Cortese¹⁴

Affiliations

¹ IRCCS Mondino Foundation, Pavia, Italy.
² Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
³ Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
⁴ Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology and The National Hospital for Neurology and Neurosurgery, London, UK; Department of Neurology and Neurosurgery, Montreal Neurological Hospital and Institute, McGill University, Montreal, QC, Canada.
⁵ Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology and The National Hospital for Neurology and Neurosurgery, London, UK.
⁶ Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology and The National Hospital for Neurology and Neurosurgery, London, UK; Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
⁷ IRCCS Mondino Foundation, Pavia, Italy; Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology and The National Hospital for Neurology and Neurosurgery, London, UK.
⁸ Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology and The National Hospital for Neurology and Neurosurgery, London, UK; William Harvey Research Institute, Queen Mary University of London, London, UK.
⁹ Department of Neurogedengerative Disease, UCL Queen Square Institute of Neurology and The National Hospital for Neurology and Neurosurgery, London, UK.
¹⁰ Department of Human Genetics and Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA.
¹¹ Department of Neurology and Neurosurgery, Montreal Neurological Hospital and Institute, McGill University, Montreal, QC, Canada.
¹² Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology and The National Hospital for Neurology and Neurosurgery, London, UK.
¹³ Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Institute of Medical Genomics, International University of Health and Welfare, Chiba, Japan.
¹⁴ Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology and The National Hospital for Neurology and Neurosurgery, London, UK; Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy. Electronic address: [email protected].

PMID: 38876750
DOI: 10.1016/S1474-4422(24)00167-4

Abstract

Nucleotide repeat expansions in the human genome are a well-known cause of neurological disease. In the past decade, advances in DNA sequencing technologies have led to a better understanding of the role of non-coding DNA, that is, the DNA that is not transcribed into proteins. These techniques have also enabled the identification of pathogenic non-coding repeat expansions that cause neurological disorders. Mounting evidence shows that adult patients with familial or sporadic presentations of epilepsy, cognitive dysfunction, myopathy, neuropathy, ataxia, or movement disorders can be carriers of non-coding repeat expansions. The description of the clinical, epidemiological, and molecular features of these recently identified non-coding repeat expansion disorders should guide clinicians in the diagnosis and management of these patients, and help in the genetic counselling for patients and their families.

Publication types

Review

MeSH terms

DNA Repeat Expansion / genetics
Diagnosis, Differential
Humans
Nervous System Diseases* / diagnosis
Nervous System Diseases* / genetics