A novel <i>TFG</i> c.793C&gt;G mutation in a Chinese pedigree with Charcot‐Marie‐Tooth disease 2

Wu, Dingwen; Li, Yanfang; Yin, Xinzhen; Zhang, Baorong

doi:10.1002/brb3.1724

Cited by 3 publications

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“…The typical clinical phenotype of CMT 2 includes foot deformity, areflexia, symmetricity, distal weakness, amyotrophy of the lower limbs, and hypoesthesia, which is more pronounced in the upper limbs than in the lower limbs, notwithstanding the genetic heterogeneity ( 18 ). Clinical features of CMT 2 usually include slowly progressive symmetrical muscle atrophy and weakness, predominantly in the distal limbs ( 19 ), which was also present in our case, but beyond sensory impairment. Brisk reflexes, extensor plantar responses, and asymmetrical muscle involvement can be considered parts of the CMT 2 phenotype ( 8 ).…”

Section: Discussionsupporting

confidence: 59%

Case Report: Early-Onset Charcot-Marie-Tooth 2N With Reversible White Matter Lesions Repeatedly Mimicked Stroke or Encephalitis

et al. 2022

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IntroductionCharcot-Marie-Tooth (CMT) disease is a rare group of peripheral neuropathies with high clinical and genetic heterogeneity. CMT type 2N (CMT 2N) is a rare subtype of CMT with few clinical reports. The clinical presentation mimics that of other diseases, frequently leading to misdiagnoses. We present a case of CMT 2N with reversible white matter lesions (WMLs), which repeatedly mimicked stroke or encephalitis. We include a literature review to the improve management of this disease.Case DescriptionAn 8-year-old boy was admitted to the hospital with slurred speech and limb weakness that had persisted for 1 day. Physical examination revealed lethargy, dysarthria, and a positive bilateral Babinski sign. Cerebrospinal fluid (CSF) analysis showed no abnormalities. Brain magnetic resonance imaging (MRI) revealed symmetrical abnormal signal areas in the paraventricular white matter and corpus callosum. The patient was suspected of having viral encephalitis and recovered rapidly after treatment.He was hospitalized 3 years later for limb weakness, barylalia, and facial paralysis persisting for 1 day. MRI showed an abnormal signal in the bilateral corona radiata. He was suspected of having a stroke or encephalitis. He was completely recovered after treatment.After a second 3-year span, he was admitted for another stroke-like episode. Physical examination revealed facial-lingual hemiparesis, mild atrophy of the left thenar muscle, decreased muscle strength in the extremities, and disappearance of the tendon reflex. MRI revealed more pronounced abnormal signals in the bilateral centrum semiovale and corpus callosum. Antibodies against autoimmune encephalitis were negative. A nerve conduction velocity (NCV) study showed motor and sensory four-limb nerve demyelination with axonal damage, most notably at the distal end. His symptoms were resolved after active treatment. A follow-up MRI showed the complete disappearance of the abnormal white matter signal. Whole exon sequencing showed a heterozygous mutation [c.2093C > T(p.Ser698Phe)] in the alanyl-tRNA synthetase 1 gene (AARS1). His mutation, clinical features, and electrophysiological testing led to a diagnosis of CMT 2N.DiscussionEarly-Onset CMT 2N with reversible WMLs can often mimic stroke or encephalopathy. Affected individuals may show an atypical posterior reversible encephalopathy syndrome (PRES) on MRI. Careful family history assessment, physical examination, nerve conduction studies, MRIs, and genetic testing are essential for early diagnosis. Further studies are required to confirm these findings.

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Section: Discussionsupporting

confidence: 59%

Case Report: Early-Onset Charcot-Marie-Tooth 2N With Reversible White Matter Lesions Repeatedly Mimicked Stroke or Encephalitis

et al. 2022

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“… 12 Furthermore, a possibly pathogenic p.P265A (c.793C > G) mutation was recently reported in patients with CMT2. 13 These three CMT‐related mutations are localized to the P/Q‐rich domain, and the substituted amino acids are highly conserved throughout evolution (Figure 2B ).…”

Section: Resultsmentioning

confidence: 99%

TFG mutation induces haploinsufficiency and drives axonal Charcot–Marie–Tooth disease by causing neurite degeneration

et al. 2022

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Aims TFG‐related axonal Charcot–Marie–Tooth (CMT) disease is a late‐onset, autosomal dominant, hereditary motor, and sensory neuropathy characterized by slowly progressive weakness and atrophy of the distal muscles. The objective of this study was to determine the common pathogenic mechanism of TFG‐related CMT type 2 (CMT2) caused by different mutations and establish a direct association between TFG haploinsufficiency and neurodegeneration. Methods Three individuals carrying the TFG p.G269V mutation but with varying disease durations were studied. The effect of the p.G269V mutation was confirmed by analyzing protein samples extracted from the blood of two individuals. The functional consequences of both CMT2 mutant gene products were evaluated in vitro. The effect of TFG deficiency in the nervous system was examined using zebrafish models and cultured mouse neurons. Results Overexpression of p.G269V TFG failed to enhance soluble TFG levels by generating insoluble TFG aggregates. TFG deficiency disrupted neurite outgrowth and induced neuronal apoptosis both in vivo and in vitro and further impaired locomotor capacity in zebrafish, which was consistent with the phenotype in patients. Wnt signaling was activated as a protective factor in response to TFG deficiency. Conclusion CMT2‐related TFG mutation induces TFG haploinsufficiency within cells and drives disease by causing progressive neurite degeneration.

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A novel TFG c.793C>G mutation in a Chinese pedigree with Charcot‐Marie‐Tooth disease 2

Yin

et al. 2020

Brain and Behavior

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A novel TFG c.793C>G mutation in a Chinese pedigree with Charcot‐Marie‐Tooth disease 2

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 3 publications

References 21 publications

Case Report: Early-Onset Charcot-Marie-Tooth 2N With Reversible White Matter Lesions Repeatedly Mimicked Stroke or Encephalitis

Case Report: Early-Onset Charcot-Marie-Tooth 2N With Reversible White Matter Lesions Repeatedly Mimicked Stroke or Encephalitis

TFG mutation induces haploinsufficiency and drives axonal Charcot–Marie–Tooth disease by causing neurite degeneration

A novel TFG c.793C>G mutation in a Chinese pedigree with Charcot‐Marie‐Tooth disease 2

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