Exome sequencing and SNP analysis detect novel compound heterozygosity in fatty acid hydroxylase-associated neurodegeneration

Tyler Mark Pierson, Dimitre R. Simeonov, Murat Sincan, David A. Adams, Thomas Markello, Gretchen Golas, Karin Fuentes-Fajardo, Nancy F. Hansen, Praveen F. Cherukuri, Pedro Cruz, James C. Mullikin, Craig Blackstone, Cynthia Tifft, Cornelius F. Boerkoel, William A. Gahl

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)476-479
Number of pages4
JournalEuropean Journal of Human Genetics
Volume20
Issue number4
DOIs
StatePublished - Apr 2012

Keywords

  • deletion analysis
  • exome sequencing
  • fatty acid 2-hydroxylase
  • fatty acid hydroxylase-associated neurodegeneration
  • neuropathy

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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