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Identification and clinical characterization of Charcot-Marie-Tooth disease type 1C patients with LITAF p.G112S mutation

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Abstract

Background

Charcot-Marie-Tooth disease type 1C (CMT1C) is a rare subtype associated with LITAF gene mutations. Until now, only a few studies have reported the clinical features of CMT1C.

Objective

This study was performed to find CMT1C patients with mutation of LITAF in a Korean CMT cohort and to characterize their clinical features.

Methods

In total, 1,143 unrelated Korean families with CMT were enrolled in a cohort. We performed whole exome sequencing to identify LITAF mutations, and examined clinical phenotypes including electrophysiological and MRI features for the identified CMT1C patients.

Results

We identified 10 CMT1C patients from three unrelated families with p.G112S mutation in LITAF. The frequency of CMT1C among CMT1 patients was 0.59%, which is similar to reports from Western populations. CMT1C patients showed milder symptoms than CMT1A patients. The mean CMT neuropathy score version 2 was 7.7, and the mean functional disability scale was 1.0. Electrophysiological findings showed a conduction block in 22% of affected individuals. Lower extremity MRIs showed that the superficial posterior and anterolateral compartments of the calf were predominantly affected.

Conclusions

We found a conduction block in Korean CMT1C patients with p.G112S mutation and first described the characteristic MRI findings of the lower extremities in patients with LITAF mutation. These findings will be helpful for genotype–phenotype correlation and will widen understanding about the clinical spectrum of CMT1C.

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Availability of data and materials

All raw genetic and clinical data generated or analyzed during this study are available upon request to the corresponding author.

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Acknowledgements

This work was supported by grants from the National Research Foundation (2019R1A2C1087547, 2020M3H4A1A03084600, and 2021R1A4A2001389) and the Korean Health Technology R&D Project, Ministry of Health and Welfare (HI14C3484 and HI20C0039), Republic of Korea.

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Author notes

  1. Jaehong Park, Hyun Su Kim and Hye Mi Kwon authors contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Korea

    Jaehong Park, Hye Mi Kwon, Jiah kim, Soo Hyun Nam & Byung-Ok Choi

  2. Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, 06351, Seoul, Korea

    Hyun Su Kim

  3. Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Korea

    Soo Hyun Nam & Byung-Ok Choi

  4. Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Korea

    Soo Hyun Nam & Byung-Ok Choi

  5. Department of Biological Sciences, Kongju National University, 56 Gongjudaehak-ro, Gongju, 32588, Korea

    Na Young Jung, Ah Jin Lee & Ki Wha Chung

  6. Department of Neurology, College of Medicine, Myongji Hospital, Hanyang University, Goyang, Korea

    Young Hee Jung

  7. Department of Neurology, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, 05278, Korea

    Sang Beom Kim

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  1. Jaehong Park
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Contributions

B-OC and KWC planned and supervised this study. NYJ, AJL, and SHN performed the molecular genetic work. HMK. JK, and JP performed the clinical and neuroimaging work. NYJ, AJL, and KWC interpreted genetic data and conducted the statistical analyses. B-OC collected the participant samples and information. JP, HMK, B-OC, and KWC wrote the manuscript. All the co‑authors read and approved the final version of the manuscript.

Corresponding authors

Correspondence to Ki Wha Chung or Byung-Ok Choi.

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Competing interests

The authors have no competing interests to declare.

Ethics approval and consent to participate

This study was approved by the Institutional Review Boards of Sungkyunkwan University, Samsung Medical Center (2014–08-057–002), and Kongju National University (KNU-IRB-2018–62). Written informed consent was obtained from all participants.

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Not applicable.

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Park, J., Kim, H.S., Kwon, H.M. et al. Identification and clinical characterization of Charcot-Marie-Tooth disease type 1C patients with LITAF p.G112S mutation. Genes Genom 44, 1007–1016 (2022). https://doi.org/10.1007/s13258-022-01253-w

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  • DOI: https://doi.org/10.1007/s13258-022-01253-w

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