Prepair 1000+

Gene: NAXE

Green List (high evidence)

Early-onset progressive encephalopathy with brain edema and/or leukoencephalopathy-1 (PEBEL1) is an autosomal recessive severe neurometabolic disorder characterized by rapidly progressive neurologic deterioration that is usually associated with a febrile illness. Affected infants tend to show normal early development followed by acute psychomotor regression with ataxia, hypotonia, respiratory insufficiency, and seizures, resulting in coma and death in the first years of life. Brain imaging shows multiple abnormalities, including brain edema and signal abnormalities in the cortical and subcortical regions.
Reported in >5 unrelated families.
One case reported novel biallelic GGGCC repeat expansion as long as ~200 repeats in the NAXE promoter region using long-read sequencing. In addition to a marked reduction in the RNA and protein, there was a marked reduction in nascent RNA in the promoter, suggesting transcriptional suppression. CpG hypermethylation was observed in the repeat region. Genetic analyses determined that homozygosity in the patient was due to maternal chromosome 1 uniparental disomy (UPD). PMID: 39455596

Created: 27 Dec 2024, 5:02 a.m. | Last Modified: 27 Dec 2024, 5:02 a.m.

Panel Version: 1.904

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, MIM #617186

Publications

• PMID: 27122014
• 27616477
• 31758406
• 34678889
• 35637064
• 39455596