Novel ABCD1 Variants in X-Linked Adrenoleukodystrophy

Abstract

X-linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disorder caused by mutations in the ABCD1 gene. We reported the clinical features and genetic findings of 17 X-ALD patients. Fifteen variants were identified, including five novel mutations: c.700dupC (p.Arg234Profs*67), c.743G>A (p.Gly248Asp), c.1469_1471delTGG (p.Val490del), c.1577C>A (p.Thr526Lys), and c.1658T>C (p.Leu553Pro), which were reported for the first time in X-ALD patients. Functional analysis confirmed the pathogenicity of novel variants at the protein and subcellular localization level. The p.Arg234Profs*67 mutant protein was undetectable, likely due to NMD-mediated mRNA degradation. This study expands the mutation spectrum and clinical profile of X-ALD, suggesting a potential correlation between the extent of protein dysfunction and disease severity.

Keywords: ABCD1 gene; X‐linked adrenoleukodystrophy (X‐ALD); adrenomyeloneuropathy (AMN); childhood cerebral ALD (CCALD); protein stability.