Null variants in DYSF result in earlier symptom onset

Area of Science:

• Neurology
• Genetics
• Molecular Biology

Background:

• Dysferlinopathy is a group of inherited neuromuscular disorders caused by mutations in the DYSF gene.
• Understanding the genotype-phenotype correlation is crucial for diagnosis and management.

Purpose of the Study:

• To investigate the clinical, laboratory, and genetic characteristics of Korean patients with dysferlinopathy.
• To clarify the genotype-phenotype correlation in dysferlinopathy.

Main Methods:

• Retrospective review of 101 patients from 96 unrelated families with pathogenic DYSF variants.
• Analysis of clinical phenotypes, including age at onset and muscle strength.
• Comparison of clinical outcomes between patients with null/null and null/missense DYSF variants.

Main Results:

• Miyoshi myopathy was the most common initial phenotype (50 patients).
• Null/null DYSF variants were associated with significantly earlier symptom onset (median 20 vs. 29 years) and lower muscle strength scores compared to null/missense variants.
• Nine novel DYSF variants were identified among the 38 observed variants.

Conclusions:

• This study is the first to report that null variants in the DYSF gene lead to an earlier symptom onset than missense variants in dysferlinopathy.
• The findings highlight the importance of variant type (null vs. missense) in predicting disease progression and severity.