In-frame deletion variant of ABCD1 in a sporadic case of adrenoleukodystrophy

TL;DR

A rare genetic deletion in the ABCD1 gene is found to cause adrenoleukodystrophy in a man with adult-onset symptoms.

Contribution

The study confirms the pathogenicity of a previously uncertain in-frame deletion variant in ABCD1 through biochemical and clinical analysis.

Findings

The in-frame deletion c.1469_71delTGG in ABCD1 was confirmed to be pathogenic through biochemical and clinical evaluation.

Functional assessment of in-frame deletions is crucial for accurate diagnosis in adrenoleukodystrophy.

Abstract

Adrenoleukodystrophy (ALD), an X-linked leukodystrophy caused by pathogenic variants in ABCD1, exhibits a broad range of phenotypes from childhood-onset cerebral forms to adult-onset adrenomyeloneuropathy (AMN). We report a rare in-frame ABCD1 deletion c.1469_71delTGG (p.Val490del) in a man with AMN. Although this variant has been interpreted as ‘uncertain significance’ in ClinVar, biochemical analysis along with clinical evaluation confirmed the pathogenicity of this variant, underscoring the importance of functional assessment of in-frame deletions.

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