Abstract
Fatty acid hydroxylase-associated neurodegeneration due to fatty acid 2-hydroxylase deficiency presents with a wide range of phenotypes including spastic paraplegia, leukodystrophy, and/or brain iron deposition. All previously described families with this disorder were consanguineous, with homozygous mutations in the probands. We describe a 10-year-old male, from a non-consanguineous family, with progressive spastic paraplegia, dystonia, ataxia, and cognitive decline associated with a sural axonal neuropathy. The use of high-throughput sequencing techniques combined with SNP array analyses revealed a novel paternally derived missense mutation and an overlapping novel maternally derived ∼28-kb genomic deletion in FA2H. This patient provides further insight into the consistent features of this disorder and expands our understanding of its phenotypic presentation. The presence of a sural nerve axonal neuropathy had not been previously associated with this disorder and so may extend the phenotype.
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Acknowledgements
We are grateful to the patients and the parents of the family for their cooperation. We thank Shannon McNeil, Ronald Austin, Jose Salas, Chevalia Robinson, Joy Bryant, and Cheryl Hipple, Eva Baker, Bryan Brooks, Barrington Burnett, Kenneth Fischbeck, Roxanne Fischer, Hiroko Hama, Tanya Lehky, Joseph Snow, Gilbert Vezina, Lynne Wolfe, and Sandra Yang, for administrative, clinical and technical assistance, and critical analysis. This work was supported by the NIH Undiagnosed Diseases Program and the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health.
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Pierson, T., Simeonov, D., Sincan, M. et al. Exome sequencing and SNP analysis detect novel compound heterozygosity in fatty acid hydroxylase-associated neurodegeneration. Eur J Hum Genet 20, 476–479 (2012). https://doi.org/10.1038/ejhg.2011.222
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DOI: https://doi.org/10.1038/ejhg.2011.222
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