Analysis of GFAP variants in UK Biobank suggests underdiagnosis or incomplete penetrance of adult-onset Alexander disease.

ABSTRACT:

Background

Alexander disease is an autosomal dominant leukodystrophy caused by heterozygous pathogenic variants in the glial fibrillar acidic protein (GFAP) gene. Although increasingly recognised, there is evidence that Alexander disease, particularly later-onset disease, is significantly underdiagnosed and its true prevalence is unknown (the only population-based prevalence was estimated at one in 2.7 million). Using the extensive UK Biobank dataset, we analysed the frequency of pathogenic and likely pathogenic variants, GFAP variants, within the UK population and identified clinical and radiological phenotypes linked to these variants.

Methods

Pathogenic, likely pathogenic and GFAP variants of uncertain significance were identified in the UK Biobank whole-exo

SUBMITTER: Gagliardi D 

PROVIDER: S-EPMC12322464 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature