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

Background: Charcot-Marie-Tooth disease (CMT) is among the most common group of inherited neuromuscular diseases. mutations were demonstrated to cause autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). However, there have been few case reports regarding to and gene mutation to CMT in Vietnamese patients, and the diagnosis of and 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 and genes to confirm the presence of selected variants on their parents, we identified a novel missense variant (inherited from the mother) in an autosomal dominant heterozygous state, and two recessive variants (, causing missense variant, and , 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 variant and biallelic variants.

Conclusion: We concluded that this novel variant is likely benign, and biallelic mutation ( and ) 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 related and -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.