A novel single-point mutation of NEFH and biallelic SACS mutation presenting as intermediate form Charcot-Marie-Tooth: A case report in Vietnam

Anh Tuan Truong; Anh Thi Lan Luong; Linh Hai Nguyen; Huong Van Nguyen; Diep Ngoc Nguyen; Ngoc Thi Minh Nguyen

doi:10.25259/SNI_803_2022

A novel single-point mutation of NEFH and biallelic SACS mutation presenting as intermediate form Charcot-Marie-Tooth: A case report in Vietnam

Surg Neurol Int. 2022 Nov 25:13:553. doi: 10.25259/SNI_803_2022. eCollection 2022.

Authors

Anh Tuan Truong¹, Anh Thi Lan Luong², Linh Hai Nguyen³, Huong Van Nguyen³, Diep Ngoc Nguyen⁴, Ngoc Thi Minh Nguyen²

Affiliations

¹ Department of Clinical Medicine, Nam Dinh University of Nursing, Nam Dinh, Vietnam.
² Department of Medical Biology and Genetics, Hanoi Medical University, Hanoi, Vietnam.
³ Department of Neurology, Hanoi Medical University, Hanoi, Vietnam.
⁴ Institute of Theoretical and Applied Research (ITAR), School of Medicine and Pharmacy, Duy Tan University, Da Nang, Vietnam.

Abstract

Background: Charcot-Marie-Tooth disease (CMT) is among the most common group of inherited neuromuscular diseases. SACS mutations were demonstrated to cause autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). However, there have been few case reports regarding to NEFH and SACS gene mutation to CMT in Vietnamese patients, and the diagnosis of CMT and ARSACS in the clinical setting still overlapped.

Case description: We report two patients presenting with sensorimotor neuropathy without cerebellar ataxia, spasticity and other neurological features, being diagnosed with intermediate form CMT by electrophysiological and clinical examination and neuroimaging. By whole-exome sequencing panel of two affected members, and PCR Sanger on NEFH and SACS genes to confirm the presence of selected variants on their parents, we identified a novel missense variant NEFH c.1925C>T (inherited from the mother) in an autosomal dominant heterozygous state, and two recessive SACS variants (SACS c.13174C>T, causing missense variant, and SACS c.11343del, causing frameshift variant) (inherited one from the mother and another from the father) in these two patients. Clinical and electrophysiological findings on these patients did not match classical ARSACS. To the best of our knowledge, this is the first case report of two affected siblings diagnosed with CMT carrying both a novel NEFH variant and biallelic SACS variants.

Conclusion: We concluded that this novel NEFH variant is likely benign, and biallelic SACS mutation (c.13174C>T and c.11343del) is likely pathogenic for intermediate form CMT. This study is also expected to emphasize the current knowledge of intermediate form CMT, ARSACS, and the phenotypic spectrum of NEFH-related and SACS-related disorders. We expect to give a new understanding of CMT; however, further research should be conducted to provide a more thorough knowledge of the pathogenesis of CMT in the future.

Keywords: Autosomal recessive spastic ataxia of Charlevoix-Saguenay; Intermediate Charcot-Marie-Tooth disease; NEFH; Novel variant; SACS.

Publication types

Case Reports