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- Title
Cerebello-brainstem dominant form of X-linked adrenoleukodystrophy with intrafamilial phenotypic variability.
- Authors
Jae-Hwan Choi; Hyun Sung Kim; Eun Hye Oh; Jae Hyeok Lee; Chong Kun Cheon
- Abstract
Objectives: This study aimed to describe the clinical and radiological characteristics of a cerebello-brainstem dominant form of X-linked adrenoleukodystrophy (X-ALD). Methods: Three affected members from a family with cerebellar ataxia received full neurological, laboratory and radiological examinations. Genetic diagnoses were confirmed using whole-exome sequencing and protein structural modeling. Results: All affected members presented with slurred speech, ataxia, and spasticity, but showed obvious differences in phenotypic severity and radiological findings. The levels of very long-chain fatty acids (VLCFA) were elevated in each member, while only one had adrenal dysfunction. Genetic analysis identified a hemizygous missense mutation (c.887A>G, p.Tyr296Cys) of the ATP-binding cassette subfamily D member 1 gene (ABCD1) in all affected members, which is likely to destabilize the overall structure of the ABCD1 protein. Conclusions: We report a cerebello-dominant form of X-ALD caused by a missense variant in ABCD1. This report highlights intrafamilial phenotypic variability in X-ALD.
- Subjects
ADRENOLEUKODYSTROPHY; PHENOTYPIC plasticity; CEREBELLAR ataxia; AMINO acid sequence; MISSENSE mutation; MULTIPLE human abnormalities
- Publication
Frontiers in Neurology, 2022, Vol 13, p1
- ISSN
1664-2295
- Publication type
Article
- DOI
10.3389/fneur.2022.999419