CMT-SARS1

SARS1 | 2023

What Is CMT-SARS1?

CMT-SARS1 is a type of CMT caused by autosomal dominant mutations in the SARS1 gene. This gene provides instructions for making seryl-tRNA synthetase, an enzyme that attaches the amino acid serine to its transfer RNA during protein synthesis. Mutations in the SARS1 gene disrupt this function, leading to impaired nerve signal transmission.

CMT-SARS1 is autosomal dominant, meaning that just one of the gene’s two copies needs a mutation to cause this subtype.

Clinical Features

The age of symptom onset in CMT-SARS1 is variable, ranging from childhood to adulthood. Symptoms typically begin in the lower extremities and progress over time to involve the upper limbs. Nerve conduction studies usually show slowed conduction velocities, consistent with a demyelinating form of CMT.

CMT-SARS1 symptoms may include:

  • Weakness in the feet and lower legs
  • Muscle atrophy
  • Foot drop
  • Reduced or absent reflexes
  • Reduced sensation
  • A steppage-style walking pattern
  • Foot deformities, including high arches, and hammertoes (clawed toes)
  • Progressive involvement of the hands and forearms
  • Difficulty with fine motor skills and manual dexterity
  • Additional symptoms not listed here

Disease Course

CMT-SARS1 shows wide variability in severity and progression. Some individuals are mildly affected, while others develop a more severe disease. Disease progression is generally slow, and life expectancy is not reduced.

Clinical Basics

Subtype
CMT-SARS1

Classification
Unclassified Subtypes

Neuropathy Type
Demyelinating

Inheritance Pattern
autosomal dominant

Genetic Context

HGNC-Approved Gene Symbol
SARS1

Gene Full Name
seryl-tRNA synthetase 1

HGNC Gene Alias(es)
SARS, SERS, SERRS

Chromosome
1p13.3

Zygosity of Responsible Variant
Heterozygous

Variant Mechanism

Unknown

Details

Mechanistic basis:
Unresolved

Confidence:
Low

Prediction:
The evidence does not converge on a mechanism for CMT-SARS1: this ultra-rare dominant subtype is known from a single de novo report (Record et al. 2023) with no functional dissection, and the mutant seryl-tRNA synthetase has been assayed neither for aminoacylation nor for the conformational opening that generates neomorphic interactions in other dominant tRNA-synthetase CMTs. Lost serylation capacity and a toxic gain acquired by the mutant enzyme both remain in play.

Rationale:
Mechanism is heterogeneous across the dominant tRNA-synthetase CMTs, interference in some and neomorphic activity in others, so what holds for one gene does not transfer to SARS1. Absent aminoacylation, supplementation, or model-organism data on the de novo alleles, the mechanism stays open.

ClinVar Pathogenic Variants

View SARS1 ClinVar Variants

SARS1 OMIM Entry

SARS1 OMIM

More Info

CMT-SARS1 Research Opportunity

CMT Natural History Study

Original Discovery Publication

Publication Title

SARS1 (SerRS) causing de novo Dominant Charcot-Marie-Tooth Disease with Slow Conduction

Authors

Record, C. J., Skorupinksa, M., Zuchner, S., Blake, J., & Reilly, M. M.

Publication Date
September 14, 2023

Updated: July 18, 2026 | By: K. Raymond

The Dorsal Root

More From The Dorsal Root


A Name That Does Too Much Work

Jean-Martin Charcot's name appears throughout medicine, but nowhere does it create more confusion than in the foot. Learn why the CMT foot and Charcot neuroarthropathy, also known as Charcot foot, share a name yet differ in how they develop, appear, and are managed.


When Medicine Lost Its Compass

Evidence failed not because it was wrong, but because it was weaponized. I lived the downstream effects of that failure for more than a decade. This is what happens when medicine forgets that data always ends in a human being.


Error 404: Gene Not Found

CMT genetic testing often fails to identify the cause of the disease, even when comprehensive panels are used. Here, we discuss why this happens, what genetic tests can and cannot do, and why a negative result still matters.