SIGMAR1 gene-related neuromuscular disorders - what do we know?

Area of Science:

• Neurology
• Genetics
• Rare Diseases

Background:

• Distal hereditary motor neuropathies (dHMNs) are a diverse group of rare neuromuscular disorders.
• Jerash-type dHMN (dHMNJ) is a subtype caused by SIGMAR1 gene mutations, presenting with distal weakness and pyramidal signs.

Purpose of the Study:

• To investigate the pathogenicity of a specific SIGMAR1 variant (c.247T>C) in a patient with dHMNJ.
• To highlight the role of SIGMAR1 in neuromuscular disorders and support broader genetic testing.

Main Methods:

• Literature review of MEDLINE and PubMed databases.
• Analysis of genetic testing results from a 12-year-old boy with dHMNJ symptoms.

Main Results:

• Identified a homozygous c.247T>C (p.Phe83Leu) SIGMAR1 variant in the patient.
• This variant, previously of uncertain significance, is now supported as pathogenic.

Conclusions:

• SIGMAR1-related disorders (SIGMAR1-RD) present a spectrum including dHMN and juvenile ALS.
• The Sigma-1 receptor is crucial for cellular stress responses and neuronal survival.
• The c.247T>C SIGMAR1 variant is pathogenic, necessitating wider genetic screening for hereditary motor neuropathies.