X-linked adrenoleukodystrophy in a chimpanzee due to an ABCD1 mutation reported in multiple unrelated humans

Julian Curiel, Steven Jeffrey Steinberg, Sarah Bright, Ann Snowden, Ann B. Moser, Florian Eichler, Holly A. Dubbs, Joseph G. Hacia, John J. Ely, Jocelyn Bezner, Alisa Gean, Adeline Vanderver

Research output: Contribution to journalArticle

Abstract

Background X-linked adrenoleukodystrophy (X-ALD) is a genetic disorder leading to the accumulation of very long chain fatty acids (VLCFA) due to a mutation in the ABCD1 gene. ABCD1 mutations lead to a variety of phenotypes, including cerebral X-ALD and adrenomyeloneuropathy (AMN) in affected males and 80% of carrier females. There is no definite genotype-phenotype correlation with intrafamilial variability. Cerebral X-ALD typically presents in childhood, but can also present in juveniles and adults. The most affected tissues are the white matter of the brain and adrenal cortex. MRI demonstrates a characteristic imaging appearance in cerebral X-ALD that is used as a diagnostic tool. Objectives We aim to correlate a mutation in the ABCD1 gene in a chimpanzee to the human disease X-ALD based on MRI features, neurologic symptoms, and plasma levels of VLCFA. Methods Diagnosis of X-ALD made using MRI, blood lipid profiling, and DNA sequencing. Results An 11-year-old chimpanzee showed remarkably similar features to juvenile onset cerebral X-ALD in humans including demyelination of frontal lobes and corpus callosum on MRI, elevated plasma levels of C24:0 and C26:0, and identification of the c.1661G > A ABCD1 variant. Conclusions This case study presents the first reported case of a leukodystrophy in a great ape, and underscores the fidelity of MRI pattern recognition in this disorder across species.

Original languageEnglish (US)
Pages (from-to)130-133
Number of pages4
JournalMolecular Genetics and Metabolism
Volume122
Issue number3
DOIs
StatePublished - Nov 1 2017
Externally publishedYes

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Adrenoleukodystrophy
Pan troglodytes
Magnetic resonance imaging
Mutation
Fatty Acids
Genes
Plasmas
Pattern recognition
Brain
Blood
Inborn Genetic Diseases
Corpus Callosum
Adrenal Cortex
Tissue
Hominidae
Genetic Association Studies
Frontal Lobe
Demyelinating Diseases
Lipids
Imaging techniques

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology

Cite this

X-linked adrenoleukodystrophy in a chimpanzee due to an ABCD1 mutation reported in multiple unrelated humans. / Curiel, Julian; Steinberg, Steven Jeffrey; Bright, Sarah; Snowden, Ann; Moser, Ann B.; Eichler, Florian; Dubbs, Holly A.; Hacia, Joseph G.; Ely, John J.; Bezner, Jocelyn; Gean, Alisa; Vanderver, Adeline.

In: Molecular Genetics and Metabolism, Vol. 122, No. 3, 01.11.2017, p. 130-133.

Research output: Contribution to journalArticle

Curiel, J, Steinberg, SJ, Bright, S, Snowden, A, Moser, AB, Eichler, F, Dubbs, HA, Hacia, JG, Ely, JJ, Bezner, J, Gean, A & Vanderver, A 2017, 'X-linked adrenoleukodystrophy in a chimpanzee due to an ABCD1 mutation reported in multiple unrelated humans', Molecular Genetics and Metabolism, vol. 122, no. 3, pp. 130-133. https://doi.org/10.1016/j.ymgme.2017.08.012
Curiel, Julian ; Steinberg, Steven Jeffrey ; Bright, Sarah ; Snowden, Ann ; Moser, Ann B. ; Eichler, Florian ; Dubbs, Holly A. ; Hacia, Joseph G. ; Ely, John J. ; Bezner, Jocelyn ; Gean, Alisa ; Vanderver, Adeline. / X-linked adrenoleukodystrophy in a chimpanzee due to an ABCD1 mutation reported in multiple unrelated humans. In: Molecular Genetics and Metabolism. 2017 ; Vol. 122, No. 3. pp. 130-133.
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AU - Moser, Ann B.

AU - Eichler, Florian

AU - Dubbs, Holly A.

AU - Hacia, Joseph G.

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AU - Vanderver, Adeline

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N2 - Background X-linked adrenoleukodystrophy (X-ALD) is a genetic disorder leading to the accumulation of very long chain fatty acids (VLCFA) due to a mutation in the ABCD1 gene. ABCD1 mutations lead to a variety of phenotypes, including cerebral X-ALD and adrenomyeloneuropathy (AMN) in affected males and 80% of carrier females. There is no definite genotype-phenotype correlation with intrafamilial variability. Cerebral X-ALD typically presents in childhood, but can also present in juveniles and adults. The most affected tissues are the white matter of the brain and adrenal cortex. MRI demonstrates a characteristic imaging appearance in cerebral X-ALD that is used as a diagnostic tool. Objectives We aim to correlate a mutation in the ABCD1 gene in a chimpanzee to the human disease X-ALD based on MRI features, neurologic symptoms, and plasma levels of VLCFA. Methods Diagnosis of X-ALD made using MRI, blood lipid profiling, and DNA sequencing. Results An 11-year-old chimpanzee showed remarkably similar features to juvenile onset cerebral X-ALD in humans including demyelination of frontal lobes and corpus callosum on MRI, elevated plasma levels of C24:0 and C26:0, and identification of the c.1661G > A ABCD1 variant. Conclusions This case study presents the first reported case of a leukodystrophy in a great ape, and underscores the fidelity of MRI pattern recognition in this disorder across species.

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