X‑linked adrenoleukodystrophy caused by maternal ABCD1 mutation and paternal X chromosome inactivation

Li,Zhen; Lai,Guangrui

doi:10.3892/etm.2022.11502

X‑linked adrenoleukodystrophy caused by maternal ABCD1 mutation and paternal X chromosome inactivation

Authors:
- Zhen Li
- Guangrui Lai
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Affiliations: Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China, Department of Clinical Genetics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China
Published online on: July 12, 2022 https://doi.org/10.3892/etm.2022.11502
Article Number: 565
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

X‑linked adrenoleukodystrophy (X‑ALD) is the most common peroxisomal disorder. It is caused by defects in the ATP‑binding cassette subfamily D member 1 (ABCD1) gene, resulting in impaired peroxisomal β‑oxidation of very‑long‑chain fatty acids (VLCFAs). As an X‑linked recessive disease, female X‑ALD carriers are typically asymptomatic. In the present study, a 7‑year‑old girl was diagnosed with cerebral ALD. Brain magnetic resonance imaging revealed asymmetric demyelination of bilateral white matter. Plasma VLCFAs level showed a substantial increase. Whole exome and Sanger sequencing revealed an ABCD1 c.919C>T (p.Q307X) heterozygous pathogenic mutation, which was inherited from the asymptomatic mother. X chromosome inactivation (XCI) analysis revealed that the normal paternal X chromosome was almost completely inactivated. Thus, the maternal ABCD1 mutation and paternal XCI were responsible for causing the disease in the patient. XCI may be one reason female X‑ALD carriers can be symptomatic.

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