Genetic modifiers and non-Mendelian aspects of CMT

Dana M. Bis-Brewer, Sarah Fazal, Stephan Züchner

Research output: Contribution to journalReview article

Abstract

Charcot-Marie-Tooth (CMT) neuropathies are amongst the most common inherited diseases in neurology. While great strides have been made to identify the genesis of these diseases, a diagnostic gap of 30–60% remains. Classic models of genetic causation may be limited to fully close this gap and, thus, we review the current state and future role of alternative, non-Mendelian forms of genetics in CMT. Promising synergies exist to further define the full genetic architecture of inherited neuropathies, including affordable whole-genome sequencing, increased data aggregation and clinical collaboration, improved bioinformatics and statistical methodology, and vastly improved computational resources. Given the recent advances in genetic therapies for rare diseases, it becomes a matter of urgency to diagnose CMT patients with great fidelity. Otherwise, they will not be able to benefit from such therapeutic options, or worse, suffer harm when pathogenicity of genetic variation is falsely evaluated. In addition, the newly identified modifier and risk genes may offer alternative targets for pharmacotherapy of inherited and, potentially, even acquired forms of neuropathies.

Original languageEnglish (US)
Article number146459
JournalBrain Research
Volume1726
DOIs
StatePublished - Jan 1 2020

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Tooth
Modifier Genes
Genetic Models
Neurology
Rare Diseases
Computational Biology
Causality
Genetic Therapy
Virulence
Genome
Drug Therapy
Therapeutics

Keywords

  • Charcot-Marie-Tooth
  • Genetic modifiers
  • Multilocus
  • Non-mendelian inheritance

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Cite this

Genetic modifiers and non-Mendelian aspects of CMT. / Bis-Brewer, Dana M.; Fazal, Sarah; Züchner, Stephan.

In: Brain Research, Vol. 1726, 146459, 01.01.2020.

Research output: Contribution to journalReview article

Bis-Brewer, Dana M. ; Fazal, Sarah ; Züchner, Stephan. / Genetic modifiers and non-Mendelian aspects of CMT. In: Brain Research. 2020 ; Vol. 1726.
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