First case with RANBP2 biallelic mutation and severe acute necrotizing encephalopathy phenotype

Area of Science:

• Genetics
• Neurology
• Molecular Biology

Background:

• Familial acute necrotizing encephalopathy (ANE) is a rare, severe neurological disorder.
• ANE can manifest after common viral infections across various life stages.
• Understanding the genetic underpinnings of familial ANE is crucial for diagnosis and treatment.

Observation:

• This study details the clinical findings of two siblings diagnosed with ANE.
• Whole-exome sequencing was performed on the index case to identify the genetic cause.
• Sanger sequencing confirmed the identified genetic variant.

Findings:

• A homozygous p.I656V variant in the RANBP2 gene was identified in the index case.
• The same variant was found to be heterozygous in the parents.
• These findings implicate biallelic mutations in RANBP2 as a potential cause of ANE.

Implications:

• Biallelic RANBP2 mutations may lead to early-onset ANE with a severe prognosis.
• Increased penetrance of RANBP2 variants could be associated with familial ANE.
• Further research into RANBP2's role in ANE is warranted for improved clinical outcomes.