Novel ABCD1 Gene Mutation in Adrenomyeloneuropathy with Hypoplasia and Agenesis of the Corpus Callosum

Yusen Qiu; Ling Xin; Yuyao Wang; Yanyan Yu; Keji Zou; Qian Zhou; Yunqing Chen; Shuyun Chen; Min Zhu; Daojun Hong

doi:10.1159/000490248

Novel ABCD1 Gene Mutation in Adrenomyeloneuropathy with Hypoplasia and Agenesis of the Corpus Callosum

Neurodegener Dis. 2018;18(2-3):156-164. doi: 10.1159/000490248. Epub 2018 Jul 2.

Authors

Yusen Qiu^{1

2}, Ling Xin³, Yuyao Wang², Yanyan Yu^{1

2}, Keji Zou^{1

2}, Qian Zhou^{1

2}, Yunqing Chen^{1

2}, Shuyun Chen^{1

2}, Min Zhu², Daojun Hong¹

Affiliations

¹ Department of Neurology, Peking University People's Hospital, Beijing, China.
² Department of Neurology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
³ Department of Health, Exercise Science and Recreation Management, University of Mississippi, Oxford, Mississippi, USA.

PMID: 29966135
DOI: 10.1159/000490248

Abstract

Background: Adult adrenomyeloneuropathy (AMN) is caused by mutations in the ABCD1 gene. Some pure AMN patients develop cerebral demyelination late in life. However, hypoplasia and agenesis of the corpus callosum (CC) has never been reported in AMN patients.

Objective: To describe a new clinical variant of AMN that is possibly caused by a novel ABCD1 gene mutation.

Methods: A total of 10 members in an X-linked inherited family were examined. The age at onset, progression of disability, and clinical manifestations were collected. Blood tests of the index case were conducted in an academic hospital. Cerebral and spinal MRI was performed in 4 affected members using a Siemens 3.0-T or Hitachi 1.0-T MR scanner. Whole-exome sequencing was conducted in the index case, which was subsequently validated by Sanger sequencing in the family.

Results: The patients displayed typical degenerative spastic paraparesis and peripheral sensorimotor neuropathy with some intrafamilial variations. In addition to neurological deficits, all male patients displayed alopecia since adolescence. Furthermore, an increase in plasma long-chain fatty acids was observed. Based on these presentations, adult AMN was diagnosed for the patients. Intriguingly, cerebral MRI showed multiple types of hypoplasia and agenesis of the CC including anterior remnant CC agenesis, truncated corpus and splenium, anterior remnant CC agenesis along with thin corpus and splenium. Whole-exome sequencing revealed a nonsense mutation (c.231G>A) which results in a truncated protein product (p.W77X) that might be nonfunctional. No other mutations associated with alopecia or hypoplasia and agenesis of the CC were identified in the exome-sequencing database.

Conclusion: In addition to the typical symptoms such as spastic myelopathy, cognitive impairment, mixed neuropathy, and alopecia, AMN patients can also display hypoplasia and agenesis of the CC, which was not described in the other AMN patients reported before.

Keywords: Adrenoleukodystrophy; Adrenomyeloneuropathy; Alopecia; Corpus callosum, hypoplasia and agenesis; Spastic paraplegia.

Publication types

Case Reports
Research Support, Non-U.S. Gov't

MeSH terms

ATP Binding Cassette Transporter, Subfamily D, Member 1 / genetics*
ATP-Binding Cassette Transporters / genetics*
Adrenoleukodystrophy / genetics*
Adult
Age of Onset
Agenesis of Corpus Callosum / genetics*
Corpus Callosum / metabolism
Humans
Magnetic Resonance Imaging / methods
Male
Mutation / genetics*
Pedigree
Phenotype

Substances

ABCD1 protein, human
ATP Binding Cassette Transporter, Subfamily D, Member 1
ATP-Binding Cassette Transporters