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Pathogenic PSAT1 variants and autosomal recessive axonal Charcot–Marie–Tooth disease with ichthyosis

      Abstract

      Objective

      Biallelic pathogenic phosphoserine aminotransferase 1 (PSAT1) variants generally cause a severe phenotype predominantly involving central nervous system. Here, for the first time, we report two patients harboring pathogenic PSAT1 variants only manifested as polyneuropathy and ichthyosis.

      Methods

      Two patients from unrelated families presenting with polyneuropathy and ichthyosis were enrolled. Whole exome sequencing was performed to identify possible disease-causing variants. Their clinical, electrophysiological, imaging, biochemical, and pathological changes were in detail assessed and investigated.

      Results

      Homozygous variants c.43G>C and compound heterozygous variants c.112A>C and c.43G>C in PSAT1 were identified in the patients 1 and 2, respectively. Nerve conduction studies revealed preserved or mildly slow of motor nerve conduction velocities of the median nerves in the two patients, while the compound motor action potential in patient 1 was severely decreased. Brain MRI of the two patients found no abnormalities. Median nerve enlargement was observed on ultrasound in patient 1. Both patients had normal level of serine and glycine in plasma and cerebrospinal fluid. Sural nerve biopsy found severe loss of myelinated fibers. Electron microscopy revealed neurofilaments accumulation and mitochondrial aggregation in axons. Both variants in PSAT1 were classified as likely pathogenic or pathogenic variants according to the standard guidelines.

      Conclusions

      Our study confirms that pathogenic PSAT1 variants can cause a mild phenotype, predominantly as autosomal recessive axonal Charcot–Marie–Tooth disease.

      Keywords

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