ATP6V1B2-related epileptic encephalopathy.

Area of Science:

• Genetics
• Neuroscience
• Molecular Biology

Background:

• ATP6V1B2 gene encodes a lysosomal proton pump subunit crucial for acid hydrolase function.
• Pathogenic variants in ATP6V1B2 are linked to Zimmermann-Laband syndrome 2 (intellectual disability/malformations) and dominant deafness onychodystrophy (malformations without cognitive issues).
• Epilepsy is variable in ZLS2, absent in DDOD, but common in related syndromes (ZLS1, ZLSL).

Observation:

• A case report details an infant presenting with severe epileptic encephalopathy, microcephaly, and profound developmental delay.
• Whole-exome sequencing identified a novel de novo loss-of-function variant in the ATP6V1B2 gene in this infant.
• This clinical presentation differs from previously described ATP6V1B2 phenotypes.

Findings:

• The novel de novo loss-of-function variant in ATP6V1B2 is associated with severe early-onset epileptic encephalopathy.
• This finding expands the phenotypic spectrum of ATP6V1B2-related disorders.
• ATP6V1B2 is identified as a new gene implicated in early-onset epileptic encephalopathy.

Implications:

• This study broadens the understanding of ATP6V1B2 gene function and its role in neurological disorders.
• It highlights the importance of genetic testing, including whole-exome sequencing, for diagnosing complex neurodevelopmental conditions.
• The identification of ATP6V1B2 as an epileptic encephalopathy gene contributes to the growing genetic landscape of severe early-onset epilepsy.