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 language | English (US) |
|---|---|
| Article number | 146459 |
| Journal | Brain Research |
| Volume | 1726 |
| DOIs | |
| State | Published - Jan 1 2020 |
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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 journal › Review article
}
TY - JOUR
T1 - Genetic modifiers and non-Mendelian aspects of CMT
AU - Bis-Brewer, Dana M.
AU - Fazal, Sarah
AU - Züchner, Stephan
PY - 2020/1/1
Y1 - 2020/1/1
N2 - 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.
AB - 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.
KW - Charcot-Marie-Tooth
KW - Genetic modifiers
KW - Multilocus
KW - Non-mendelian inheritance
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UR - http://www.scopus.com/inward/citedby.url?scp=85072979119&partnerID=8YFLogxK
U2 - 10.1016/j.brainres.2019.146459
DO - 10.1016/j.brainres.2019.146459
M3 - Review article
C2 - 31525351
AN - SCOPUS:85072979119
VL - 1726
JO - Brain Research
JF - Brain Research
SN - 0006-8993
M1 - 146459
ER -