Unraveling ALS: A Genetic Look at SOD1 in India

In India, a recent study has delved into the genetic roots of a specific type of amyotrophic lateral sclerosis (ALS), focusing on the SOD1 gene. ALS is a challenging disease that affects nerve cells.

Key Findings

• Study Scope: The research involved 765 individuals, of which 37 were found to have SOD1-related ALS (approximately 4.8% of the group).
• Familial Cases: These 37 individuals came from 33 families, accounting for a significant 24.2% of familial ALS cases in the study.
• Gender Distribution: Most participants were men, with a ratio of 1.64:1.
• Symptom Onset: Symptoms typically appeared at an average age of 41.9 years, though this varied widely.
• Genetic Variants: The study identified 23 different harmful or likely harmful SOD1 gene changes, including four new variants never before documented.

Notable Discoveries

• Homozygous Variants: Six patients had two copies of the same harmful gene change (homozygous variants), leading to earlier disease onset.
• Symptom Presentation: 67.6% of participants first noticed symptoms in their legs, with a form of ALS primarily affecting the lower motor neurons.
• Survival Analysis: Certain gene changes, such as H47R, V88M, and I152N, were linked to longer survival. However, those with juvenile onset (very young diagnosis) had shorter lifespans.

Significance of the Study

This is the first large-scale study of SOD1-related ALS in India, revealing that the genetic landscape of ALS in India is unique, with a higher prevalence of homozygous harmful gene variants. The findings also help connect specific gene changes to disease progression and symptoms.